Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 INTRANASAL DIHYDROPYRIDINE COMPOSITIONS AND METHODS CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No.63/403,061, filed September 1, 2022, the contents of which are incorporated by reference herein in their entirety for all purposes. BACKGROUND Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Its defining clinical features are bradykinesia, rigidity or tremor. These motor symptoms are attributable to the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that innervate the basal ganglia (Berg et al., 2014; Hornykiewicz, 2002). The vulnerability of these neurons to the genetic and environmental risk factors associated with PD, as well as to aging, is attributable to basal mitochondrial oxidant stress that damages lipids, proteins and DNA, particularly in mitochondria (Reeve et al., 2014; Surmeier and Schumacker, 2013; Surmeier et al., 2017a). This stress results from sustained stimulation of mitochondrial oxidative phosphorylation (OXPHOS) to supply the adenosine triphosphate (ATP) needed for regenerative activity, transmitter release and the anabolic demands of their massive axonal arbor (Bolam and Pissadaki, 2012; Graves et al., 2019; Pacelli et al., 2015). In SNc dopaminergic neurons, as well as in many other at-risk neurons, mitochondrial OXPHOS is driven by Ca2+ entry through plasma membrane ion channels having a pore- forming Cav1 .3 subunit (Guzman et al., 2018; Surmeier et al., 2017a). As a consequence, inhibiting Cav1.3 Ca2+channels lowers oxidant stress and mitochondrial damage in at-risk neurons and, in animal models, decreases the sensitivity to genetic mutations and environmental toxins linked to PD (Surmeier et al., 2017a)[Guzman, 2018]. In humans, use of FDA-approved dihydropyridines, which are selective negative allosteric modulators (NAMs) of Cav1.3 Ca2+channels, has been associated with a decreased risk of developing PD (Becker et al., 2008; Gudala et al., 2015; Lee et al., 2014; Pasternak et al., 2012; Ritz et al., 2010). Substance abuse disorders, including opioid use disorder, are chronic, relapsing disorders driven in part by strong associations formed between drugs and sensory cues experienced during drug intake, such as places, people, and interoceptive drug cues, i.e., subjective effects caused by drugs themselves (Wise et al., 2011; Robinson et al., 2014; Volkow et al., 2010). Addictive drugs are thought to hijack synaptic plasticity mechanisms in key brain circuits involved in reward learning, especially the mesolimbic dopaminergic system 290639686 1 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 comprising the ventral tegmental area (VTA) and its projections to the nucleus accumbens and other limbic structures (Hyman et al., 2006; Kauer et al., 2007; Luthi et al., 2014). As such, powerful and enduring memories of drug-related cues are formed, overshadowing other cues associated with non-drug rewards and driving continued drug use as well as relapse after a period of abstinence. Therefore, reducing the strength of drug cue memories by manipulating the underlying synaptic plasticity mechanisms may decrease relapse. Ca2+ channels with either a Cav1.2 or Cav1.3 pore-forming subunit are expressed by neurons in the brain and control a variety of processes, including the synaptic plasticity thought to underlie memory (Lipscombe et al., 2004). Indeed, systemic administration of inhibitors of these channels disrupts the acquisition of drug-induced conditioned place preference (CPP) Pani et al., 1991; Pucilowski et al., 1995; Biala et al., 1996; Pucilowski et al., 1993)23-26. More specifically, local inhibition of these channels in ventral tegmental area (VTA) and SNc dopaminergic neurons impairs the recollection of cues associated with cocaine consumption and attenuates cue-induced cocaine-seeking (Addy et al., 2018; Degoulet et al., 2016). In patients suffering from opioid use disorder (OUD) that are being maintained on methadone, oral administration of 5 or 10 mg (but not 2.5 mg) isradipine abolished the withdrawal-inducing effects of naloxone (an opioid antagonist) (Oliveto et al., 2004). In OUD patients treated with buprenorphine, oral administration of isradipine reduced the rate of illicit opioid use and reduced the frequency and intensity of cravings (Kumar et al., 2020). Finally, in a related form of drug abuse, oral administration of isradipine reduced the subjective and reinforcing effects of methamphetamine, including drug-liking, elation, and drug preference (Johnson et al., 1999). Within the class of dihydropyridines including amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine, clevidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, levamlodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, and pranidipine, are negative allosteric modulators (NAMs) of Ca2+ channels with a Cav1.1, Cav1.2 or Cav1.3 pore-forming subunit. While many of the aforementioned dihydropyridine calcium channel inhibitors have been used for treatment of hypertension in humans, certain dihydropyridine calcium channel inhibitors have been used to great angina in humans, and one dihydropyridine calcium channel inhibitor, nimodipine, known to pass the blood-brain barrier, is used to prevent cerebral vasospasm. These agents typically act on vascular smooth muscle causing arterial vasodilation and reducing blood pressure. 290639686 2 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 The antihypertensive effect resulting from administration of these agents necessitates a systemic delivery so that the agents can act on the arteries. To provide such systemic delivery, oral formulations have been developed for human therapeutic use for many of these agents, including felodipine, isradipine, nicardipine hydrochloride, nifedipine, nimodipine, and nisoldipine. Intravenous formulations have been prepared for nicardipine hydrochloride and clevidipine. Certain dihydropyridine calcium channel inhibitors such as isradipine and felodipine have been formulated for oral administration in immediate release and extended release forms. As currently marketed, dihydropyridine calcium channel inhibitors are prescribed for use over periods of days, weeks, months, or years. Adverse effects associated with administration of these dihydropyridine calcium channel inhibitors is documented in the FDA labels for these agents. Systemic administration of these agents has resulted in increased incidence or severity of adverse effects including dizziness, dyspnea, peripheral edema, fatigue, flushing, headache, palpitations, tachycardia, diarrhea, constipation and gastrointestinal disturbances. Intranasal administration of therapeutic agents has been used in the treatment of rhinitis, migraines, seizures, severe pain, and opioid overdose. Azelastine hydrochloride has been marketed as a liquid composition for the treatment of seasonal allergic rhinitis. Zolmitriptan has been marketed as a liquid composition for the treatment of acute migraine. Sumatriptan succinate has been marketed as a powder and liquid composition for the treatment of migraine. Diazepam has been marketed as a liquid composition for the treatment of seizures. Ketorolac tromethamine has been marketed as a liquid composition for short term management of moderate to moderately severe pain. Naloxone hydrochloride has been marketed as a liquid composition for treatment of opioid overdose. Intranasal compositions are typically administered with single use or multi-use devices such as those manufactured by Aptar, Illinois, USA, OptinNose US, Pennsylvania, USA, or Becton Dickinson, New Jersey, USA, or those described in US patents 7,975,690, 10,124,132, 10,478,574, 10,765,602, 10,894,133, all incorporated herein by reference. Although certain dihydropyridines have been approved by the FDA for various clinical indications, they have not been approved for treatment of neurodegenerative diseases, like PD, or for substance abuse disorders, like OUD. In both cases, there is a major unmet medical need for new therapeutic options. For PD, there are no approved disease-modifying drugs, despite the growing human and societal burden of the disease. For OUD and other substance abuse disorders, which also poses a growing human and societal burden, there are very limited and marginally effective treatment strategies that reduce cravings and prevent relapse. 290639686 3 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 SUMMARY The inventors have discovered that the therapeutic potential for treating Parkinson’s disease and substance abuse disorder with certain dihydropyridines can be enhanced by delivering said dihydropyridines by the intranasal route. For instance, while clinical data with isradipine suggests that targeting Cav1.3 channels may be a viable strategy for treating PD and substance abuse disorder, the application of isradipine for the treatment of PD and substance abuse disorder has major liabilities. For instance, dose-limiting cardiovascular side effects (e.g. peripheral edema) are associated with all oral formulations of isradipine. This is due to the fact that isradipine (and other dihydropyridines) do not distinguish between Cav1 subunits; thus, they also inhibit Cav1.2 channels in cardiac and smooth muscle cells. Inhibition of peripheral Cav1.2 channels results in vasodilation and reduced blood pressure. However, for PD, substance abuse, and other disorders of the central nervous system (CNS), the relevant target is Cav1.3, which is mainly expressed in the brain. Thus, inhibition of Cav1.2 channels and peripheral side-effects associated with isradipine (and other dihydropyridines) limits dosing to a range that is less than optimal for CNS disorders. At the maximum tolerated dose of 10 mg/day – the minimum oral dose required to reach threshold protection in PD – 35% of patients experienced peripheral edema, which increased to up to 60% at higher doses (Parkinson Study Group). Furthermore, while our analyses indicate that an extended release (ER) formulation of isradipine may be more efficacious than an immediate release (IR) formulation, studies in both cardiovascular patients and PD patients demonstrate that the ER formulation is associated with a higher incidence of peripheral edema (Parkinson Study Group, DynaCirc). Thus, the present inventors believe that an intranasal route of delivery may maximize brain levels of isradipine to effectively inhibit Cav1.3, while minimizing systemic exposure and reducing Cav1.2 activity to decrease cardiovascular side effects. The present disclosure describes compositions and methods for administering a therapeutically effective dose of a dihydropyridine calcium channel inhibitor selected from the group consisting of azelnidipine, barnidipine, benidipine, cilnidipine, clevidipine, efonidipine, felodipine, isradipine, lacidipine, lercandipine, manidipine, nicardipine, nimodipine, nisoldipine, and nitrendipine, including salts thereof, individual isomers and mixtures thereof, and amorphous and crystalline forms of the aforementioned dihydropyridine calcium channel inhibitors (a “DHP”) to treat a subject diagnosed with Parkinson’s disease. Intranasal administration of a DHP according to the present disclosure provides a therapeutically effective concentration of said DHP in the CNS while reducing the concentration of said DHP in body 290639686 4 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 (as determined by plasma concentration of said DHP). The CNS concentration of said DHP (as measured in the CSF or in brain tissue) may be increased above the levels that may be achieved by oral administration of a similar dose of said DHP. Intranasal administration of a DHP to a subject diagnosed with Parkinson’s disease provides one or more of the following: a) a delay in the onset of dopaminergic therapy, b) a reduction in the progression rate for Parkinson’s disease, c) an increase in the time between adjustments in dopaminergic therapy dosing, d) a reduction in the effective dose for dopaminergic therapy, e) an improvement in the UPDRS score for said subject, f) an improvement in Part III of the UPDRS score for said subject. The intranasal administration of a DHP according to the present disclosure reduces the incidence or severity of one or more adverse effects associated with oral administration of said DHP calcium channel inhibitor. The intranasal administration of a DHP according to the present disclosure reduces the incidence or severity of one or more adverse effects selected from the group consisting of atrial fibrillation, chest pain, dizziness, dyspnea, epistasis, fatigue, flushing, headache, heart failure, hypotension, myocardial infarction, palpitations, peripheral edema, syncope, tachycardia, ventricular fibrillation, constipation, diarrhea, and gastrointestinal disturbances relative to the incidence or severity observed for oral administration of said DHP according to the FDA label. The intranasal administration of a DHP according to the present disclosure reduces the incidence or severity of one or more of cardiovascular side effects selected from the group consisting of atrial fibrillation, chest pain, dyspnea, epistasis, heart failure, hypotension, myocardial infarction, peripheral edema, syncope, tachycardia, and ventricular fibrillation relative to the incidence or severity observed for oral administration of said DHP according to the FDA label. In some embodiments, DHPs are useful in the treatment of substance-related disorders when administered intranasally. The present disclosure describes compositions and methods for administering a therapeutically effective dose of a DHP to treat a subject diagnosed with substance-related disorder. Intranasal administration of a DHP according to the present disclosure provides a therapeutically effective concentration of said DHP in the CNS while reducing the concentration of said DHP in body (as determined by plasma concentration of said DHP). The CNS concentration of said DHP (as measured in the CSF or in brain tissue) may be increased above the levels that may be achieved by oral administration of a similar dose of said DHP. Intranasal administration of a DHP to a subject diagnosed with a substance- related disorder provides one or more of the following thing: a) reduction in the incidence and intensity of craving, b) reduction in the incidence of illicit drug use, c) increase in the number of patients achieving drug abstinence, d) decrease in the incidence of overdoses, e) decrease in 290639686 5 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 the incidence of death from overdose. The intranasal administration of a DHP according to the present disclosure reduces the incidence or severity of one or more adverse effects associated with oral administration of said DHP. The intranasal administration of a DHP according to the present disclosure reduces the incidence or severity of one or more adverse effects selected from the group consisting of dizziness, dyspnea, peripheral edema, fatigue, flushing, headache, palpitations, tachycardia, diarrhea, constipation, and gastrointestinal disturbances. In one aspect, the present disclosure is directed to a unit dose for intranasal administration of a therapeutically effective amount of isradipine, wherein said unit dose is in a powder, liquid, or suspension form, wherein said unit dose comprises 0.1 to 5.0 mg of isradipine. In some embodiments, the unit dose comprises 0.4 to 4.0 mg of isradipine. In some embodiments, the unit dose is in a powder form. In some embodiments, the unit dose is in a liquid form. In some embodiments, the unit dose is in a suspension form. In some embodiments, the unit dose is administered with a device. In some embodiments, the unit dose is delivered with a device which dispenses said unit dose upon actuation. In some embodiments, actuation is mechanical or electronic. In one aspect, the present disclosure is directed to a method of treating a subject in need of isradipine therapy, comprising intranasal administration of a therapeutically effective amount of a formulation comprising isradipine to said subject formulated for intranasal administration, wherein said formulation is in a powder, liquid, or suspension form, wherein said therapeutically effective amount of said formulation comprises 0.1 to 5.0 mg of isradipine. In some embodiments, the therapeutically effective amount of said formulation comprises 0.4 to 4.0 mg of isradipine. In some embodiments, the formulation is in a powder form. In some embodiments, the formulation is in a liquid form. In some embodiments, the formulation is in a suspension form. In some embodiments, the formulation is administered with a device. In some embodiments, the device dispenses a therapeutically effective amount of said formulation upon actuation. In some embodiments, the actuation is mechanical or electronic. In some embodiments, the formulation is administered one to 4 times per day. 290639686 6 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 In some embodiments, the formulation is administered once or twice per day. In some embodiments, the formulation is administered to said subject once per day. In some embodiments, administering the formulation to said subject provides a mean steady state plasma concentration in said subject of 0.1 to 2.0 ng/ml. In some embodiments, administering the formulation provides a CSF concentration in said subject of 0.2 to 2.2 ng/ml. In some embodiments, administering the formulation provides a CSF concentration in the subject of 0.2 to 10 ng/mL, e.g., 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL. In some embodiments, the subject has been diagnosed with a neurodegenerative disease selected from the group consisting of ALS, Alzheimer’s disease, corticobasal degeneration, dementia with Lewy Bodies, Lewy Body disease, multiple system atrophy, Parkinson’s disease, or supranuclear palsy. In some embodiments, the subject has been diagnosed with Parkinson’s disease. In some embodiments, the subject has been diagnosed with a substance use disorder. In some embodiments, the subject has been diagnosed with a use disorder of a drug selected from the group consisting of alcohol, amphetamines, cocaine, methamphetamine, opioids, and nicotine. In some embodiments, the subject has been diagnosed with opioid use disorder. The contents of all references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated herein in their entireties by reference. The references cited herein are not admitted to be prior art to the application. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 provides a chart showing the brain and plasma concentrations of isradipine in mice following the intranasal administration of two formulations of isradipine. FIG.2 provides a chart showing the concentration-time profile of isradipine in the brain and plasma of mice following the intrasnasal formulation of a formulation of isradipine. DETAILED DESCRIPTION The present disclosure is directed to intranasal administration of certain DHPs to patients in need thereof. The present inventors have discovered that intranasal administration of DHPs, e.g., isradipine, may arrest or slow the progression of neurological diseases such as 290639686 7 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Parkinson’s disease. Without wishing to be bound by theory, the present inventors believe that the administration of DHPs, e.g., isradipine, may be useful in the treatment of disorders such as PD wherein the efficacy of said therapeutic agents is dependent upon achieving a high ratio of central nervous system (CNS) concentration to plasma concentration. In some embodiments, the methods of intranasal administration and compositions for intranasal administration disclosed herein effectuate a higher ratio of CNS concentration to plasma concentration than can be achieved with an oral formulation or method of oral administration. As used herein, therapeutic efficacy for a patient with Parkinson’s disease may be: i) reduced rate of disease progression (relative to the rate of progression during a comparable time period such as 3 months or 6 months for said patient prior to treatment), ii) decreased quantity of dopaminergic therapeutic required for symptom management (relative to similar patients not receiving said DHP), iii) an increase in the time between adjustments in dopaminergic therapy dosing, iv) delayed onset of need for dopaminergic therapy (relative to similar patients not receiving said DHP treatment), v) improved United Parkinson’s Disease Rating Scale (UPDRS) total score (relative to similar patients not receiving said DHP treatment), or vi) improved UPDRS part III score (relative to similar patients not receiving said DHP treatment). In some embodiments, therapeutic efficacy may involve extending the window of utility of dopaminergic therapy, such that dopaminergic therapy can be administered for a longer period of time without inducing debilitating side effects such as motor complications. In some embodiments, the DHP is isradipine. In some embodiments the dose of isradipine is 0.05 to 20 mg. In some embodiments, the dose of isradipine is 0.1 to 5.0 mg. In some embodiments, the dose of isradipine is 0.4 to 4.0 mg. In some embodiments, the DHP is felodipine. In some embodiments the dose of felodipine is 0.05 to 20 mg. In some embodiments, the dose of felodipine is 0.1 to 5.0 mg. In some embodiments, the dose of felodipine is 0.4 to 4.0 mg. In some embodiments, intranasal administration of certain DHPs to patients in need thereof may treat substance-related disorders such as opioid use disorder. The benefits to patients diagnosed with opioid use disorder may include: i) reduction in the incidence and intensity of craving, ii) reduction in the incidence of opioid use, iii) increase in the number of patients achieving drug abstinence, iv) decrease in the incidence of overdoses, v) decrease in the incidence of death from overdose. In some embodiments, the DHP is isradipine. In some embodiments the dose of isradipine is 0.05 to 20 mg. In some embodiments, the dose of isradipine is 0.1 to 5.0 mg. In some embodiments, the dose of isradipine is 0.4 to 4.0 mg. In some embodiments, the DHP is felodipine. In some embodiments the dose of felodipine is 0.05 290639686 8 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 to 20 mg. In some embodiments, the dose of felodipine is 0.1 to 5.0 mg. In some embodiments, the dose of felodipine is 0.4 to 4.0 mg. As used herein, a substance-related disorder is a mental health disorder defined in the Diagnostic and Statistical Manual of Mental Disorders, 5 ^th Edition, Text Revision, also known as DSM-V-TR, published by the American Psychiatric Association. As used herein, opioid use disorder and dementia are mental health disorders defined in DSM-V-TR. Although certain DHPs are known to cross the blood-brain barrier after oral administration, effective oral doses of a DHP for a CNS condition such as Parkinson’s disease or opioid use disorder may not be achievable or may require dosing at levels which result in poor tolerability or increased incidence or severity of adverse effects. In one aspect, the present disclosure provides a method of administering an effective dose of a DHP to a subject diagnosed with Parkinson’s disease, Lewy Body disease, dementia with Lewy Bodies, supranuclear palsy, multiple system atrophy, or corticobasal degeneration. In one aspect, the present disclosure provides a method of administering an effective dose of a DHP to a subject diagnosed with Parkinson’s disease. In some embodiments of these aspects, the DHP is isradipine. In some embodiments of these aspects, the DHP is felodipine. In one aspect, the present disclosure provides a method of administering an effective dose of a DHP to a subject diagnosed with a substance related disorder. In one aspect of the present disclosure, the substance is chosen from a list including amphetamine, methamphetamine, cocaine, illicit opioids, prescription opioids, cannabis, alcohol, and tobacco. In one aspect, the present disclosure provides a method of administering an effective dose of a DHP to a subject diagnosed with opioid use disorder. In some embodiments of these aspects, the DHP is isradipine. In some embodiments, the DHP is felodipine. In one aspect, intranasal administration of a DHP according to the present disclosure effectuates increased CNS concentrations of said DHP as compared to the concentration of said DHP in the CNS that would have been effectuated by oral dosing of the same quantity of said DHP. In one aspect, the concentration of said DHP in the CNS is measured by the concentration in the CSF or in brain tissue. Intranasal administration according to the present disclosure provides lower systemic concentrations or lower plasma concentrations of said DHP as compared to oral dosing of the same quantity of said DHP. In one aspect, intranasal administration of a DHP enables the use of a lower daily dose of said DHP compared to oral dosing of said DHP. In some embodiments, the methods of the present disclosure provide methods of intrasnasal administration of a DHP, e.g., isradipine, to a subject that result in a CSF 290639686 9 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 concentration of the DHP, e.g., isradipine, in the subject that higher than the plasma concentration of the DHP, e.g., isradipine, in the subject. In some embodiments, the CSF concentration of the DHP, e.g., isradipine, is 2-fold to 10-fold higher than the plasma concentration of the DHP, e.g., isradipine, in the subject. In some embodiments, the CSF concentration of the DHP, e.g., isradipine, is 3-fold to 6-fold higher than the plasma concentration of the DHP, e.g., isradipine, in the subject. In some embodiments, the CSF concentration of the DHP, e.g., isradipine, is 4-fold to 5-fold higher than the plasma concentration of the DHP, e.g., isradipine, in the subject. In some embodiments, the CSF concentration of the DHP, e.g., isradipine, is 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8- fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19- fold, or 20-fold, higher than the plasma concentration of the DHP, e.g., isradipine, in the subject. In one aspect, intranasal administration of a single dose of DHP according to the present disclosure provides an increased ratio of peak CNS concentration to peak plasma concentration of said DHP relative to the ratio determined for oral administration of the same quantity of said DHP. In another aspect, the peak CNS concentration as measured in the CSF may be equal to or greater than the peak plasma concentration subsequent to intranasal administration. In one aspect, repeated intranasal administration of a DHP according to the present disclosure provides an increased ratio of peak steady state CNS concentration to peak steady state plasma concentration of said DHP relative to the ratio determined for repeated oral administration of said DHP at the same dose. The peak steady state CNS concentration as measured in the CSF may be equal to or greater than the peak steady state plasma concentration subsequent to repeated intranasal administration. The trough steady state CNS concentration as measured in the CSF may be equal to or greater than the trough steady state plasma concentration subsequent to repeated intranasal administration. In one aspect, intranasal administration of a therapeutically effective dose of a DHP provides a reduction in incidence or severity of adverse effects associated with oral administration of said DHP. In one aspect intranasal administration of a dose of a DHP therapeutically effective for treatment of a subject diagnosed with Parkinson’s disease provides a reduction in incidence or severity of adverse effects associated with oral administration of said DHP. In one aspect intranasal administration of a dose of a DHP therapeutically effective for treatment of as subject diagnosed with opioid use disorder provides a reduction in incidence or severity of adverse effects associated with oral administration of said DHP. In one aspect, the therapeutically effective intranasal dose for Parkinson’s disease or opioid use disorder is 290639686 10 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 lower than the therapeutic oral dose for Parkinson’s disease or opioid use disorder. In some embodiments of this aspect, the DHP is isradipine. In some embodiments of this aspect, the DHP is felodipine. In one aspect, intranasal administration of a DHP one to four times per day is effective for the treatment of a subject diagnosed with Parkinson’s disease. In some embodiments of this aspect, the DHP is isradipine. In some embodiments of this aspect, the DHP is felodipine. In some embodiments of this aspect, the DHP is isradipine and after intranasal administration of the DHP to said subject, the CSF concentration of isradipine is 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.4 to 2.0 ng/ml, 0.5 to 1.8 ng/ml, 0.6 to 1.5 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8- 10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL in said subject. In a preferred embodiment of this aspect, the average steady state CSF concentration of the DHP is 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.3 to 2.0 ng/ml, 0.4 to 1.8 ng/ml, 0.5 to 1.6 ng/ml, 0.6 to 1.5 ng/ml, 0.7 to 1.5 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL. In a preferred embodiment of this aspect, the DHP is isradipine and repeated intranasal administration of isradipine to said subject provides an average steady state CSF concentration of isradipine of 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.3 to 2.0 ng/ml, 0.4 to 1.8 ng/ml, 0.5 to 1.6 ng/ml, 0.6 to 1.5 ng/ml, 0.7 to 1.5 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL in said subject. In some embodiments of this aspect, intranasal administration of the DHP to said subject provides an average steady state plasma concentration (C _ave,ss ) for said DHP of 0.01 to 10 ng/ml, 0.05 to 2.2 ng/ml, 0.1 to 2.0 ng/ml, 0.2 to 1.8 ng/ml, 0.3 to 1.6 ng/ml, 0.5 to 1.5 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL. In some embodiments of this aspect, intranasal administration of the DHP to said subject proves a steady state plasma profile for said DHP in said subject characterized by a C _ave,ss that is 0.05 to 1.2 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml for at least 12, 14, 16, 18 hours per day. In some embodiments of this aspect, intranasal administration of the DHP to said subject proves a steady state plasma profile for said DHP in said subject characterized by a C _ave,ss that is 0.05 to 10 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml for at least 12, 14, 16, 18 hours per day, , 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL. In some embodiments of this aspect, the DHP is isradipine and intranasal administration of isradipine one to four times per day to said subject provides a C _ave,ss for isradipine in said subject of 0.01 290639686 11 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 to 10 ng/ml, 0.05 to 2.2 ng/ml, 0.1 to 2.0 ng/ml, 0.2 to 1.8 ng/ml, 0.3 to 1.6 ng/ml, 0.5 to 1.5 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL. In some embodiments of this aspect, the DHP is isradipine and intranasal administration of isradipine one to four times per day to said subject provides a steady state plasma profile for isradipine in said subject characterized by a C _ave,ss that is 0.05 to 1.2 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml for at least 12, 14, 16, 18 hours per day. In some embodiments of this aspect, the DHP is isradipine and intranasal administration of isradipine one to four times per day to said subject provides a steady state plasma profile for isradipine in said subject characterized by a C _ave,ss that is 0.05 to 10 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml, 2 to 4 ng/mL, 4 to 6 ng/ML, 6-8 ng/mL, 8-10 ng/mL, 1 to 2 ng/mL, 3 to 4 ng/mL, 4 to 5 ng/mL, 5 to 6 ng/mL, 6 to 7 ng/mL, 7 to 8 ng/mL, or 9 to 10 ng/mL for at least 12, 14, 16, 18 hours per day. In one aspect, intranasal administration of a DHP one to four times per day is effective for the treatment of a subject diagnosed with a substance related disorder. In a preferred embodiment of this aspect the substance related disorder is opioid use disorder. In some embodiments of this aspect, the DHP is isradipine. In some embodiments of this aspect, the DHP is felodipine. In some embodiments of this aspect, the DHP is isradipine and after intranasal administration of the DHP to said subject, the CSF concentration of isradipine is 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.4 to 2.0 ng/ml, 0.5 to 1.8 ng/ml, 0.6 to 1.5 ng/ml in said subject. In a preferred embodiment of this aspect, the average steady state CSF concentration of the DHP is 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.3 to 2.0 ng/ml, 0.4 to 1.8 ng/ml, 0.5 to 1.6 ng/ml, 0.6 to 1.5 ng/ml, 0.7 to 1.5 ng/ml. In a preferred embodiment of this aspect, the DHP is isradipine and repeated intranasal administration of isradipine to said subject provides an average steady state CSF concentration of isradipine of 0.1 to 10 ng/ml, 0.2 to 2.2 ng/ml, 0.3 to 2.0 ng/ml, 0.4 to 1.8 ng/ml, 0.5 to 1.6 ng/ml, 0.6 to 1.5 ng/ml, 0.7 to 1.5 ng/ml in said subject. In some embodiments of this aspect, intranasal administration of the DHP to said subject provides an average steady state plasma concentration (C _ave,ss ) for said DHP of 0.01 to 10 ng/ml, 0.05 to 2.2 ng/ml, 0.1 to 2.0 ng/ml, 0.2 to 1.8 ng/ml, 0.3 to 1.6 ng/ml, 0.5 to 1.5 ng/ml. In some embodiments of this aspect, intranasal administration of the DHP to said subject proves a steady state plasma profile for said DHP in said subject characterized by a C _ave,ss that is 0.05 to 1.2 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml for at least 12, 14, 16, 18 hours per day. In some embodiments of this aspect, the DHP is isradipine and intranasal administration of isradipine one to four times per day to said subject provides a C _ave,ss for isradipine in said subject of 0.01 to 2.5 ng/ml, 0.05 to 2.2 ng/ml, 0.1 to 2.0 ng/ml, 0.2 to 1.8 ng/ml, 0.3 to 1.6 ng/ml, 0.5 to 1.5 290639686 12 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 ng/ml. in some embodiments of this aspect, the DHP is isradipine and intranasal administration of isradipine one to four times per day to said subject provides a steady state plasma profile for isradipine in said subject characterized by a C _ave,ss that is 0.05 to 1.2 ng/ml, 0.1 to 1.0 ng/ml, 0.2 to 0.8 ng/ml for at least 12, 14, 16, 18 hours per day. In some embodiments of this disclosure, the total daily dose of DHP administered intranasally to a subject is 0.1 to 80 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 20 mg, 0.1 to 10 mg, 0.1 to 5.0 mg, 0.1 to 2.0 mg, 0.5 to 80 mg, 0.5 to 50 mg, 0.5 to 30 mg, 0.5 to 20 mg, 0.5 to 10 mg, 0.5 to 5.0 mg, 0.5 to 4.0 mg, 0.5 to 3.0 mg, 0.5 to 2.0 mg, 1.0 to 80 mg, 1.0 to 50 mg, 1.0 to 30 mg, 1.0 to 20 mg, 1.0 to 10 mg, 1.0 to 5.0 mg, 1.0 to 4.0 mg, 1.0 to 3.0 mg, 1.0 to 2.0 mg, 2.0 to 80mg, 2.0 to 50 mg, 2.0 to 30 mg, 2.0 to 20 mg, 2.0 to 10 mg, 2.0 to 5.0 mg, 2.0 to 4.0 mg, 5.0 to 80mg, 5.0 to 50 mg, 5.0 to 30 mg, 5.0 to 20 mg, 5.0 to 10 mg, 10 to 80 mg, 10 to 50 mg, 10 to 30 mg, 10 to 20 mg. In some embodiments of this disclosure, a dose of DHP administered intranasally to a subject is 0.05 to 20 mg, 0.05 to 15 mg, 0.05 to 10 mg, 0.05 to 5.0 mg, 0.05 to 3.0 mg, 0.05 to 2.0 mg, 0.05 to 1.0 mg, 0.05 to 0.5 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5.0 mg, 0.1 to 3.0 mg, 0.1 to 2.0 mg, 0.1 to 1.0 mg, 0.1 to 0.5 mg, 0.25 to 20 mg, 0.25 to 15 mg, 0.25 to 10 mg, 0.25 to 5.0 mg, 0.25 to 3.0 mg, 0.25 to 2.0 mg, 0.25 to 1.0 mg, 0.5 to 20 mg, 0.5 to 15 mg, 0.5 to 10 mg, 0.5 to 5.0 mg, 0.5 to 3.0 mg, 0.5 to 2.0 mg, 0.5 to 1.0 mg, 1.0 to 20 mg, 1.0 to 15 mg, 1.0 to 10 mg, 1.0 to 5.0 mg, 1.0 to 3.0 mg, 1.0 to 2.0 mg. In some embodiments, the dose is administered 4 times per day. In some embodiments, the dose is administered 3 times per day. In some embodiments, the dose is administered twice per day. In some embodiments, the dose is administered once daily. In some embodiments of this disclosure, a dose of isradipine administered intranasally to a subject is 0.02 to 10.0 mg, 0.05 to 5.0 mg, 0.05 to 3.0 mg, 0.05 to 2.0 mg, 0.05 to 1.0 mg, 0.05 to 0.5 mg, 0.1 to 5.0 mg, 0.1 to 3.0 mg, 0.1 to 2.0 mg, 0.1 to 1.0 mg, 0.1 to 0.5 mg, 0.25 to 5.0 mg, 0.25 to 3.0 mg, 0.25 to 2.0 mg, 0.25 to 1.0 mg, 0.5 to 5.0 mg, 0.5 to 3.0 mg, 0.5 to 2.0 mg, 0.5 to 1.0 mg. In some embodiments, the dose is administered 4 times per day. In some embodiments, the dose is administered 3 times per day. In some embodiments, the dose is administered twice per day. In some embodiments, the dose is administered once daily. In some embodiments of this disclosure, a dose of felodipine administered intranasally to a subject is 0.05 to 5.0 mg, 0.05 to 3.0 mg, 0.05 to 2.0 mg, 0.05 to 1.0 mg, 0.05 to 0.5 mg, 0.1 to 5.0 mg, 0.1 to 3.0 mg, 0.1 to 2.0 mg, 0.1 to 1.0 mg, 0.1 to 0.5 mg, 0.25 to 5.0 mg, 0.25 to 3.0 mg, 0.25 to 2.0 mg, 0.25 to 1.0 mg, 0.5 to 5.0 mg, 0.5 to 3.0 mg, 0.5 to 2.0 mg, 0.5 to 1.0 mg. In some embodiments, the dose is administered 4 times per day. In some embodiments, 290639686 13 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 the dose is administered 3 times per day. In some embodiments, the dose is administered twice per day. In some embodiments, the dose is administered once daily. One aspect of the disclosure is a method of intranasally administering to a patient in need thereof, a composition comprising isradipine over a period of 4 weeks, 8 weeks, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, or longer. In one aspect of repeated intranasal administration of a composition comprising isradipine to a patient with Parkinson’s disease, the UPDRS total scores for said patient over a period of 3 months, 6 months, 9 months, 12 months indicate a slower rate of decline relative to a patient with Parkinson’s disease not receiving said isradipine composition. In one aspect of repeated administration of a composition comprising isradipine to a patient with Parkinson’s disease, the UPDRS part III scores for said patient over a period of 3 months, 6 months, 9 months, 12 months indicate a slower rate of decline relative to a patient with Parkinson’s disease not receiving said isradipine composition. In one aspect of repeated administration of a composition comprising isradipine to a patient with Parkinson’s disease over a period of 3 months, 6 months, 9 months, 12 months 18 months, 24 months, 36 months, the lack of accumulated impairment indicate a reduced need for dopaminergic therapy relative to a patient with Parkinson’s disease not receiving said isradipine composition. In this aspect, a reduced need for dopaminergic therapy may be determined by a lower dose of dopaminergic therapy relative to that required for a patient not receiving said isradipine composition; alternatively, the reduced need for dopaminergic therapy may be determined by a delayed onset for the need in dopaminergic therapy relative to that required for a patient not receiving said isradipine composition. In one aspect of repeated administration of a composition comprising isradipine to a patient with Parkinson’s disease over a period of 6 months, 9 months, 12 months 18 months, 24 months, 36 months, 48 months, or longer, the lack of, or reduced incidence of, motor complications indicates an extension in the window of utility of dopaminergic therapy relative to that of a patient not receiving said isradipine composition. In one aspect, repeated intranasal administration of a composition comprising isradipine to a patient with opioid use disorder over a period of 3 months, 6 months, 9 months, 12 months results in a lower incidence and severity of cravings relative to a patient with opioid use disorder not receiving said isradipine composition. In one aspect, repeated intranasal administration of a composition comprising isradipine to a patient with opioid use disorder over a period of 3 months, 6 months, 9 months, 12 months results in a lower incidence of opioid use relative to a patient with opioid use disorder not receiving said isradipine composition. In one aspect, repeated intranasal administration of a composition comprising isradipine to a 290639686 14 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 patient with opioid use disorder over a period of 3 months, 6 months, 9 months, 12 months results in a higher likelihood of achieving abstinence from opioid use relative to a patient with opioid use disorder not receiving said isradipine composition. In one aspect, repeated intranasal administration of a composition comprising isradipine to a patient with opioid use disorder over a period of 3 months, 6 months, 9 months, 12 months results in a lower likelihood of drug overdose relative to a patient with opioid use disorder not receiving said isradipine composition. In one aspect, repeated intranasal administration of a composition comprising isradipine to a patient with opioid use disorder over a period of 3 months, 6 months, 9 months, 12 months results in a lower likelihood of death from drug overdose relative to a patient with opioid use disorder not receiving said isradipine composition. Compositions according to the present disclosure may be administered using a device to dispense the composition into the nasal cavity. Commercially available devices and those described in the patents referenced herein may be used to deliver the compositions of the disclosure. Delivery of the composition into the upper nasal cavity provides a non-systemic pathway to deliver the DHP into the CNS. Furthermore, certain devices are suitable for delivery of the DHP composition to the posterior region of the nasal cavity to achieve an increase in the delivery of said DHP to the CNS. Compositions suitable for intranasal administration of a DHP may be solids, liquids, or suspensions. In some embodiments, the DHP may be prepared as a micronized powder which may be delivered with an intranasal device without additional excipients. In such embodiments, the dose of the DHP will typically be 2 to 20 mg. In some embodiments, the DHP may be prepared as a powder composition, thus diluting the DHP in excipients such that a 5 to 25 mg quantity of the composition provides the desired DHP dose. Such powder compositions are particularly useful for administration DHP at doses of 5 mg or less. The compositions may include sugars such as mannitol or erythritol, organic buffers such as citric acid and salts thereof, inorganic buffers such as phosphoric acid and salts thereof, lubricants such as magnesium stearate, salts such as sodium chloride or potassium chloride. In some embodiments, powder compositions are prepared from components which have been micronized to ensure the particle sizes are appropriate for the delivery device and deposition in the nasal cavity. In some embodiments, the DHP is isradipine or felodipine. In some embodiments, the DHP is isradipine and the composition comprises 0.1 to 5 mg isradipine per 10 mg composition. Such compositions may be administered intranasally using a suitable device. 290639686 15 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 In some embodiments, the DHP may be prepared as a solution for intranasal administration using a spray device. The excipients for such solutions may include water, ethanol, diethylene glycol monoethyl ether, propylene glycol, cyclodextrins, polymers such as polyethylene glycol or povidone, surfactants such as dodecylphosphocholine (DPC) or lysolauroylphosphatidylcholine (LLPC), organic buffers such as citric acid and salts thereof, inorganic buffers such as phosphoric acid and salts thereof, salts such as sodium chloride or potassium chloride. Certain DHPs may require the use of an alcohol or ether to facilitate dissolution. In some embodiments, the DHP may be prepared as a suspension for intranasal administration using a suitable device. These suspensions may be useful for DHPs with very low solubility in aqueous solutions. The undissolved solids will typically be less than 10%, 5%, 2% of the total mass of the suspension. The excipients for such suspensions may include water, ethanol, sugars such as mannitol or erythritol, propylene glycol, polyethylene glycol, povidone, surfactants, organic buffers such as citric acid and salts thereof, inorganic buffers such as phosphoric acid and salts thereof, lubricants such as magnesium stearate, salts such as sodium chloride or potassium chloride. In some embodiments, the DHP may be prepared as a composition for intranasal administration that comprises polyethylene glycol (PEG), e.g., PEG 400, microcrystalline cellulose, carboxymethylcellulose sodium, dextrose, benzalkonium chloride, polysorbate 80, edetate disodium dihydrate, purified water, citric acid, e.g., citric acid monohydrate, edetate disodium, sodium hydroxide, potassium phosphate, e.g., potassium phosphate monobasic, sodium phosphate, e.g., sodium phosphate dibasic anhydrous, sodium chloride, 1-0-n-dodecyl- B-maltopyranoside (DDM), methoxypolyethylene glycol, polyethylene glycol 400, propylene glycol, ethanol., Vitamin E, benzyl alcohol, and/or dehydrated alcohol, or combinations thereof. In some embodiments, the pH of the composition is controlled. In some embodiments, the pH of che composition is 4-5, e.g., 4.5. In some embodiments, the pH of the composition is 5-7. In some embodiments, the present disclosure provides a pharmaceutical composition comprising a DHP, e.g., isradipine. In some embodiments, the pharmaceutical composition comprises a unit dose of isradipine. In some embodiments, the unit dose comprises 0.1 to 5.0 mg of isradipine. In some embodiments, the pharmaceutical composition comprises polyethylene glycol (PEG). In some embodiments, the pharmaceutical composition comprises PEG 100, PEG 400, 290639686 16 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 PEG 1000, PEG 2000, PEG, or PEG 5,000. In some embodiments, the pharmaceutical composition comprises PEG 400. In some embodiments, the pharmaceutical composition comprises an organic solvent. In some embodiments, the pharmaceutical composition comprises a polar aprotic organic solvent. In some embodiments, the pharmaceutical composition comprises N,N-dimethyl formamide (DMF). In some embodiments, the pharmaceutical composition comprises saline. In some embodiments, the pharmaceutical composition comprises a polar aprotic solvent, PEG, and saline. In some embodiments, the polar aprotic solvent, PEG, and saline are present in a ratio of about 1 part polar aprotic solvent to about 3 parts PEG to about 1 part saline. In some embodiments, the pharmaceutical composition comprises DMF, PEG 400, and saline solution. In some embodiments, the DMF, PEG 400, and saline solution are present in a ratio of about 1 part DMF to about 3 parts PEG to about 1 part saline. In some embodiments, the composition does not comprise carboxymethylcellulose. In some embodiments, liquid or suspension compositions may include preservatives. Preservatives may provide improved stability for such compositions when used in multi dose dispensing devices. In some embodiments, liquid compositions may be prepared without preservatives and sterile filtered. As used herein, the term “subject” includes human and non-human animals, as well as cell lines, cell cultures, tissues, and organs. In some embodiments, the subject is a mammal. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. In some embodiments, the subject is a human. As used herein, the term “subject in need thereof” refers to a subject having a disease or having an increased risk of developing the disease. A subject in need thereof can be one who has been previously diagnosed or identified as having a disease or disorder disclosed herein. A subject in need thereof can also be one who is suffering from a disease or disorder disclosed herein. Alternatively, a subject in need thereof can be one who has an increased risk of developing such disease or disorder relative to the population at large (i.e., a subject who is predisposed to developing such disorder relative to the population at large). A subject in need thereof can have a refractory or resistant a disease or disorder disclosed herein (i.e., a disease or disorder disclosed herein that does not respond or has not yet responded to treatment). The subject may be resistant at start of treatment or may become resistant during treatment. In some embodiments, the subject in need thereof received and failed all known effective 290639686 17 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 therapies for a disease or disorder disclosed herein. In some embodiments, the subject in need thereof received at least one prior therapy. As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable salt, polymorph or solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model. It is to be appreciated that references to “treating” or “treatment” include the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms. EXAMPLES Example 1. Intranasal administration of isradipine to nonhuman primates We designed this study to determine the brain (i.e. cerebrospinal fluid, CSF) and plasma concentrations of isradipine from two different routes of administration (oral and intranasal) in nonhuman primates (NHP). Study design: This is a cross-over study in which a group of NHPs (n=6) will receive a single oral dose of isradipine (5 mg/kg), followed by a wash-out period (1 week), and then a single intranasal dose of isradipine (5 mg/kg). After each oral and intranasal dose, plasma and CSF will be collected at varying time points, and the concentration of isradipine in plasma and CSF will be determined by liquid chromatography and mass spectrometry (LCMS). The ratio of CSF to plasma concentration of isradipine will be determined for each route of administration. Plasma and CSF sampling: CSF samples will be collected at 30 minutes, 1 hour, 1.5 hour, 2 hours, 4 hours, and 6 hours post dose. Plasma samples will be collected at 30 minutes, 1 hour, 1.5 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 12 hours post dose. 290639686 18 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Data analysis: For CSF, isradipine concentration at each time point will be tabulated, and the exposure (area under the curve, AUC) will be determined. For plasma, a non- compartmental analysis will be performed, and the following pharmacokinetic parameters will be calculated: AUC, maximum plasma concentration (C _max ), time to maximum plasma concentration (T _max ), and terminal half-life (t _1/2 ). In addition, the ratio of peak CSF to plasma concentration will be determined. Results: Higher brain, and lower plasma, concentrations are achieved with intranasal administration of isradipine compared to oral administration. Furthermore, the peak CSF-to- plasma ratio is higher with intranasal administration compared to oral administration. Example 2. Phase 1 pharmacokinetic study of intranasal isradipine in healthy volunteers This study is designed to determine the maximum tolerated dose for an intranasal formulation of isradipine, and to compare the brain and plasma levels of isradipine administered intranasally compared to orally in healthy volunteers. Study design: This is a single ascending-dose cross-over study evaluating 4 dose levels of isradipine administered intranasally and orally. The study will be conducted over four periods, wherein each period subjects will first be administered isradipine intranasally via an actuation device or orally as a tablet, followed by a 1 week wash-out, after which each subject will be crossed over to the opposite treatment (intranasal or oral). The dose (both intranasal and oral) of isradipine for each period will be (in sequence) 0.3 mg, 1 mg, 3 mg, and 10 mg. Each period will be separated by one week. The study protocol will be approved by the institutional review board and the study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Study subjects: Healthy female and male subjects between the ages of 18 and 55, inclusive, will be enrolled, with two groups of up to 36 subjects per group. Pharmacokinetic assessments: Blood samples for PK analysis will be collected predose and up to 72 hours postdose for each route of administration and in each period. CSF samples will be collected by lumbar puncture up to 24 hours postdose. No more than four CSF samples will be obtained from each subject. The concentration of isradipine in plasma and CSF will be determined by validated LCMS. Data analysis: PK parameter (C m _ax , AUC, t _1/2 ) estimates for isradipine in plasma will be calculated using standard noncompartmental methods of analysis using Phoenix WinNonlin (Pharsight, Mountain View, CA, USA). For CSF, isradipine concentration at each time point will be tabulated, and the exposure (area under the curve, AUC) will be determined. 290639686 19 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 In addition, the ratio of peak CSF to plasma concentration will be determined for each route of administration. Safety assessments: Safety will be assessed by physical examinations, clinical laboratory evaluations, vital signs, electrocardiograms (ECGs; 12-lead and telemetry), and by monitoring of treatment-emergent adverse events (TEAEs). Results: It is expected that higher CSF concentrations, lower plasma concentrations, and higher CSF/plasma ratio will be achieved with intranasal administration of isradipine compared to oral. In addition, it is expected that the incidence of cardiovascular adverse events, in particular peripheral edema, will be numerically smaller with intranasal administration compared to oral administration. Example 3. Phase 2 study of intranasal isradipine for the treatment of PD. This study assesses the safety and efficacy of two dose levels of intranasal isradipine for the treatment of Parkinson’s disease. Study design: This is a randomized, double-blind, parallel-group, placebo-controlled trial evaluating the safety and efficacy of isradipine administered by intranasal device in early stage PD patients. One hundred and twenty subjects will be randomized 1:1:1 to placebo, low dose isradipine, and high dose isradipine administered by intranasal device once or twice daily for 12 months. Subjects are not allowed to take symptomatic therapies (levodopa, dopamine agonists, or monoamine oxidase B inhibitors) while on study. Subjects requiring symptomatic therapy during the study period will be discontinued from study drug but will be encouraged to remain in the study. All subjects will be initiated on low dose intranasal isradipine or matching intranasal placebo and titrated to their assigned dosage over 4 weeks. Study subjects: Subjects will be enrolled who are women and men between 30 and 75 years old (inclusive) with a diagnosis of early PD (based on the UK brain bank diagnostic criteria) made within 3 years from randomization with Hoen and Yahr stage ≤ 2.5, and who do not require dopaminergic therapy (levodopa, dopamine agonists, or monoamine oxidase B inhibitors) and are not projected to require dopaminergic therapy for six months. Use of amantadine or anticholinergics will be allowed as long as the dose remained stable for the 3 months prior to the baseline visit. Key exclusion criteria will include a diagnosis of atypical parkinsonian syndromes; exposure to dopaminergic PD therapy within 60 days prior to enrollment or for 3 months at any point in the past; presence of cognitive dysfunction defined by a Mini–Mental Status Exam (MMSE) score ≤2; clinically significant depression as 290639686 20 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 determined by a Beck Depression Inventory II (BDI) score >15; history of exposure to typical antipsychotics or other dopamine blocking agents; history of clinically significant orthostatic hypotension, congestive heart failure, bradycardia, or other significant electrocardiography (ECG) abnormalities, laboratory abnormalities, or known medical or psychiatric comorbidities that in the investigator’s opinion would compromise participation in study. Study visits and outcome measures: Study visits will be conducted at baseline, weeks 1 and 2, and months 1, 3, 6, 9, and 12. The primary outcome measure will be change from baseline to month 12 in the United Parkinson’s Disease Rating Scale (UPDRS) total score. The UPDRS includes subscales for mental function (part I), activities of daily living (part II), and motor function (part III); scores range from 0 to 176, with higher scores indicating greater disability. Secondary outcome measures will include change from baseline to month 12 in UPDRS part III (motor) score and the number for discontinuations and time to discontinuation due to need for dopaminergic therapy. Results: Adjusted least-squares mean changes in total UPDRS scores at month 12 are significantly less for subjects treated with high dose intranasal isradipine compared to placebo, with UPDRS scores for the low dose numerically lower but not significantly different from placebo. Treatment with high dose isradipine also results in significantly lower UPDRS part III scores versus placebo, fewer discontinuations due to the need for dopaminergic therapy, and longer time to discontinuation. The number of cardiovascular adverse events, in particular peripheral edema, is not significantly different between either dose of intranasal isradipine and placebo. Example 4. Phase 2 study of intranasal isradipine for the treatment of opioid use disorder This study assesses the safety and efficacy of two dose levels of intranasal isradipine for the treatment of opioid use disorder. Study design: This is a randomized, double-blind, parallel-group, placebo-controlled trial evaluating the safety and efficacy of isradipine administered by intranasal device in patients with opioid use disorder. One hundred and twenty subjects will be stabilized on buprenorphine sublingual tablets for one week and then will be randomized 1:1:1 to placebo, low dose isradipine, and high dose isradipine administered by intranasal device once or twice daily for an additional six weeks. Subsequently, during weeks 7 to 8, subjects will undergo a 10 day buprenorphine taper, followed by a 5 day isradipine taper during week 9. 290639686 21 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Study subjects: Subjects (aged 18-65, inclusive) who meet the criteria for opioid use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and who are seeking treatment will be enrolled in the study. Subjects must submit a urine sample negative for benzodiazepines and barbiturates; meet stable orthostatic blood pressure requirements; have no unstable medical condition or stable medical condition that would interact with study medications or participation; have no history of psychosis, schizophrenia or bipolar disorder; not be pregnant, no plans to become pregnant and have adequate birth control; have no present or recent use of medications including psychoactive drugs that would have major interactions with the study drugs; have liver function tests no greater than 3 times normal with blood urea nitrogen (BUN) and creatinine within normal range; have no significant electrocardiogram (ECG) abnormalities; have no physiological dependence on alcohol or drugs other than opioids, marijuana or tobacco; and have no pre-existing severe gastrointestinal narrowing. Study visits and outcome measures: Subjects will be required to attend clinic seven days a week for 30-60 minutes for assessments and dispensation of study drug. Supervised urine drug screen samples, objective and subjective withdrawal symptom scores, self-reported adverse effects, body temperature, pupil diameter, and vital signs will be obtained three times a week. Craving assessments are conducted using a validated Visual Analog Scale which measures the number, intensity, and duration of craving episodes. Observer rated opiate withdrawal symptoms will be recorded using the Objective Opiate Withdrawal Scale (OOWS) which consists of 13 items describing withdrawal symptoms. Self-reported opioid withdrawal symptoms will be using the Opiate Withdrawal Symptoms Checklist (OWSC), which consists of 22 items describing possible opioid withdrawal symptoms rated on a scale from 0 (not at all) to 4 (very much). Self-report assessments of opioids and other drug use will be obtained at intake and on day 1 of each week using 7-day recall method instruments where participants were asked to report the amount used and method of use each day. Results: Treatment with high dose intranasal isradipine results in a significant reduction in the number of opioid-positive urine samples, a reduction in the frequency and severity of opioid cravings, and a reduction in the OWSC score. Example 5. Formulation of Isradipine Suspensions Briefly, 200 g isradipine micronized using a Sturtevant Micronizer to provide a powder with a size distribution characterized by a D90 at less than 25 microns. A carrier solution is prepared from the components in Table 1. below by mixing propylene glycol with 700 g purified water, then adding vitamin E polyethylene glycol succinate. The mixture is heated to 45°C with 290639686 22 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 continued mixing until dissolved. Methylparaben, propylparaben, propylene glycol, povidone and sodium chloride are added, and the composition mixed for an additional 10 minutes. The mixture is then cooled to 25°C. The pH of the solution is adjusted with HCl or NaOH to a pH of 5-6. The micronized isradipine (as shown in Table 1 below) is then added with vigorous mixing until the isradipine is fully dispersed in the mixture. Purified water is then added to bring the final volume to 1000 ml and the mixture is vigorously mixed for 5 minutes to provide isradipine suspensions at 2.5 mg/100 ul and 5.0 mg/100 ul (Suspension A and Suspension B, respectively). These suspensions may be dispensed into devices for intranasal administration. Table 1. Isradipine Suspension Formulations Example 6. Formulation of Felodipine Suspensions Briefly, 200 g felodipine micronized using a Sturtevant Micronizer to provide a powder with a size distribution characterized by a D90 at less than 25 microns. A carrier solution is prepared from the components in Table 2 below by mixing propylene glycol with 700 g purified water, then adding vitamin E polyethylene glycol succinate. The mixture is heated to 45°C with continued mixing until dissolved. Methylparaben, propylparaben, propylene glycol, povidone and sodium chloride are added, and the composition mixed for an additional 10 minutes. The mixture is then cooled to 25°C. The pH of the solution is adjusted with HCl or NaOH to a pH of 5-6. The micronized isradipine (as shown in Table 2 below) is then added with vigorous mixing until the isradipine is fully dispersed in the mixture. Purified water is then added to bring the final volume to 1000 ml and the mixture is vigorously mixed for 5 minutes to provide 290639686 23 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 isradipine suspensions at 2.5 mg/100 ul and 5.0 mg/100 ul (Suspension A and Suspension B, respectively). These suspensions may be dispensed into devices for intranasal administration. Table 2. Felodipine Suspension Formulations Example 7. Isradipine Dry Powder Formulations Formulations of isradipine for intranasal delivery are prepared as dry powder blends. A Sturtevant Micronizer is used to micronize 750 g isradipine to provide a powder with a size distribution characterized by a D90 at less than 20 microns. The micronized isradipine is then combined with the excipients as shown in Table 3 and each composition blended in a V- blender. The blended compositions are then micronized using a Sturtevant Micronizer to provide blends with size distributions characterized by a D10 at 1 to 10 microns, a D50 at 20 to 50 microns, and a D90 at less than 100 microns. The final blends are dispensed in dry powder dosing devices to provide 2.5 mg isradipine per 5 mg blend (Composition A), 1 mg isradipine per 5 mg blend (Composition B) or 0.25 mg isradipine per 5 mg blend (Composition C). Alternatively, the final blends are dispensed into HPMC capsules which may then be loaded into powder dosing devices for intranasal administration of the isradipine compositions. Table 3. Isradipine Dry Power Compositions 290639686 24 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Example 8. Isradipine Solutions Formulations of isradipine for intranasal delivery are prepared as solutions. A solution of isradipine is prepared by dissolving 50 g isradipine, USP, in a solution consisting of 80 g diethylene glycol monoethyl ether, NF, and 120 g purified water. Propylene glycol, USP, 12.5 g is then added to the solution with mixing and 700 g purified water is added. The pH of the solution is adjusted with hydrochloric acid or sodium hydroxide to 5.5 to 6.0, then purified water is added to bring the total mass to 1,000 g, providing a composition with an isradipine concentration of 5 mg/0.1 g. This stock solution is further diluted 1:1, 1:4, and 1:9 in purified water to provide solutions at 2.5 mg/0.1 g, 1.0 mg/0.1 g, and 0.5 mg/0.1 g, respectively. These solutions are filtered and dispensed into devices for intranasal administration. These devices, upon dispensing 0.1 g solution, deliver 2.5 mg, 1.0 mg, 0.5 mg isradipine, respectively. Example 9. Felodipine Solutions Formulations of felodipine for intranasal delivery are prepared as solutions. A solution of felodipine is prepared by dissolving 50 g felodipine, USP, in a solution consisting of 80 g diethylene glycol monoethyl ether, NF, and 120 g purified water. Propylene glycol, USP, 12.5 g is then added to the solution with mixing and 700 g purified water is added. The pH of the solution is adjusted with hydrochloric acid or sodium hydroxide to 5.5 to 6.0, then purified water is added to bring the total mass to 1,000 g, providing a composition with an isradipine concentration of 5 mg/0.1 g. This stock solution is further diluted 1:1, 1:4, and 1:9 in purified water to provide solutions at 2.5 mg/0.1 g, 1.0 mg/0.1 g, and 0.5 mg/0.1 g, respectively. These solutions are filtered and dispensed into devices for intranasal administration. These devices, upon dispensing 0.1 g solution, deliver 2.5 mg, 1.0 mg, 0.5 mg felodipine, respectively. 290639686 25 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Example 10. Pilot Pharmacokinetic study of isradipine delivered by intranasal administration in mice This study determined the brain concentrations of isradipine delivered by intranasal administration in mice. This was a parallel group study wherein 4 groups of mice received a single intranasal administration of isradipine. Two different formulations and two different doses of isradipine were assessed as follows: • Group 1: Formulation 1, 10 mg/kg • Group 2: Formulation 1, 5 mg/kg • Group 3: Formulation 2, 10 mg/kg • Group 4: Formulation 2, 5 mg/kg Formulation 1 was 0.5% carboxymethylcellulose (CMC) in saline, whereas Formulation 2 was N,N-dimethylformamide, polyethylene glycol (PEG) 400, and saline at a 2:6:2 ratio. Mice are lightly anesthetized and isradipine was administered intranasally via pipette at a total volume of up to 6 mL per nare (12 mL total per animal). At 30 minutes post administration, all animals were sacrificed and the blood and brains are harvested. The amount of isradipine in plasma and brain was determined using liquid chromatography-tandem mass spectrometry (LC- MS/MS). Results. Intranasal administration of isradipine in Formulation 1 resulted in low but detectible levels of isradipine in the brain at both doses. However, intranasal administration of isradipine at the same doses in Formulation 2 resulted in much higher concentrations in both brain and plasma compared to Formulation 1. See FIG. 1. For instance, at the 10 mg/kg dose, brain concentrations from Formulation 2 were >75-fold higher than from Formulation 1. Furthermore, for both Formulation 1 and 2, intranasal administration resulted in higher brain concentrations than in plasma. For Formulation 2 at both doses, brain concentrations were 2-3 fold higher than plasma concentrations. Finally, for Formulation 2, brain concentrations were ~15- to ~100-fold higher than the therapeutic plasma concentration determined for efficacy in mouse models of Parkinson’s disease (~7 ng/mL, Ilijic, 2011). This study demonstrated that isradipine can be administered intranasally to achieve high and therapeutic concentrations in the brain, and that specific formulations can have a profound impact on the absorption of intranasal isradipine. Furthermore, this study demonstrated that intranasal administration of isradipine provided higher brain concentrations than plasma concentrations. 290639686 26 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 Example 11. Pharmacokinetic study of isradipine delivered by intranasal administration in mice Based on these results determined in Example 10, a single formulation is selected for full pharmacokinetic (PK) evaluation in mice. Briefly, isradipine is administered intranasally or by gavage to anesthetized mice and blood will be obtained under anesthesia by cardiac puncture at the following time points: 10, 20, 30, 40, 60, 90, 120, and 180 minutes post-dose. The brains will be collected after euthanasia at the same time points. Two doses (low and high) are evaluated following intranasal and oral administration, with 3 animals for each time point. Isradipine is extracted from the blood/brain and the concentration will be determined by LC- MS/MS. The pharmacokinetics (PK) of isradipine in brain and plasma are determined by non- compartmental analysis and standard PK parameters (Cmax, tmax, AUC, t _1/2 ) are reported. In addition, the brain-to-plasma ratio for Cmax and AUC are calculated. Example 12. Efficacy of intranasal isradipine at inhibition of mitochondrial oxidant stress and turnover in dopaminergic neurons Calcium influx through neuronal Cav1 L-type calcium channels increases mitochondrial oxidant and proteostatic stress in at-risk neurons (e.g. dopaminergic neurons in the substantia nigra), which have long been thought to promote Parkinson’s disease (PD). This study evaluates the efficacy of intranasal isradipine at ameliorating mitochondrial oxidant stress and mitochondrial turnover in dopaminergic neurons. Mitochondrial turnover (mitophagy) provides a quantifiable measure of isradipine engagement with Cav1 calcium channels and the biological efficacy of this engagement in mitigating mitochondrial damage. To enable mitophagy measurements, mice receive a stereotaxic injection into the SN of an adeno-associated virus (AAV) carrying a MitoKeima expression construct under control of a tyrosine hydroxylase (TH) promoter fragment to restrict expression to dopaminergic neurons. Seven to 10 days later, mice are administered isradipine (oral and intranasal) for 7 to 10 days and midbrain slices are obtained. Fluorescence of mito-Keima is determined at excitation wavelengths of 480 nm and 561 nm. Image acquisition is achieved with SlideBook 6, and images are processed with deconvolution software. Data will be presented showing box plots summarizing the mean mito-Keima 561/480 ratio (corresponding to the relative passage of mitochondria proteins to lysosomes) from dopaminergic neurons in control and isradipine treated mice. One dose of isradipine is evaluated by each route of administration (intranasal 290639686 27 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 and oral), with 8-10 mice per dose, along with a vehicle group. The dose is based on the data from Example 10. Example 13. Pharmacokinetic study of isradipine delivered by intranasal administration in mice Based on these results determined in Example 10, Formulation 2 was selected for full pharmacokinetic (PK) evaluation in mice. Briefly, isradipine was administered intranasally and blood was obtained under anesthesia by cardiac puncture at the following time points: 0.5, 1, 3, 6, and 24 hours post-dose. The brains were collected after euthanasia at the same time points. Isradipine was administered intranasally at a dose of 10 mg/kg, with 3 animals for each time point. Isradipine was extracted from the blood/brain and the concentration were determined by LC-MS/MS. The pharmacokinetics (PK) of isradipine in brain and plasma were determined by non-compartmental analysis and standard PK parameters (Cmax, tmax, AUC) are reported. In addition, the brain-to-plasma ratio for Cmax and AUC were calculated. Results. Isradipine administered intranasally provided higher brain concentrations than plasma concentrations at all time points tested. The tmax for both brain and plasma concentrations was 0.5 hours. At Cmax, brain concentrations for isradipine was approximately 4-fold higher than plasma concentrations (800 nM [297 ng/mL] in brain versus 210 nM [78 ng/mL] in plasma). The area under the curve (AUC) in brain was approximately 8-fold greater than in plasma (326 ng*h/mL in brain versus 43 ng*hr/mL in plasma). Brain concentrations at Cmax were >40-fold higher than the therapeutic plasma concentration of isradipine determined in animal studies (7 ng/mL, Ilijic, 2011). 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EQUIVALENTS While we have described a number of embodiments of this disclosure, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this disclosure. The contents of all references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated herein in their entireties by reference. Unless otherwise defined, all technical and scientific terms used herein are accorded the meaning commonly known to one with ordinary skill in the art. The foregoing description 290639686 31 Date of Deposit: September 1 ^st , 2023 Attorney Docket No: DYAD-002/001WO-340760-2007 has been presented only for the purposes of illustration and is not intended to limit the disclosure to the precise form disclosed, but by the claims appended hereto. The references cited herein are not admitted to be prior art to the application. The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by reference. 290639686 32