19 Clinical Trials for Various Conditions
This study will be a randomized, double-blind, placebo-controlled, multicenter trial conducted to evaluate whether PP-01 mitigates the withdrawal symptoms associated with discontinuing cannabis in participants with moderate to severe Cannabis Use Disorder (CUD). The study will enroll approximately 225 participants with moderate to severe CUD and will include 5 arms, including a placebo arm, to help assess the incidence and severity of withdrawal symptoms in heavy long-term users of cannabis. Participants receive study medication for 34 days and participate in 11 visits (7 at a clinic and 4 telemedicine).
Sex and gender differences in behavioral, biological, and clinical correlates of substance use disorders are myriad, yet there exists a dearth of gender-informed treatment options. Ovarian hormones have been identified as potential mechanisms of these disparities , and recent clinical trials have begun to examine their utility as possible pharmacotherapeutic agents. The ovarian hormone progesterone has shown promise as a treatment for female cocaine and nicotine users, but has not yet been tested for cannabis. Gender differences in cannabis withdrawal, which is associated with relapse, are pronounced and several studies report more severe and impairing withdrawal symptoms in women compared to men. Developing pharmacological interventions for cannabis withdrawal remains an important priority given the significant cognitive, psychiatric, and physical consequences of heavy cannabis use.
In this study, the investigators are interested in testing how lorcaserin influences the effects of cannabis in a human laboratory model of cannabis use.
The proposed protocol is a double-blind, placebo-controlled inpatient and outpatient study,looking at the clinical treatment of cannabis use disorder. The treatment study is a total of 12 weeks. There will be two options offered to participants for week 1 of the treatment study. 1) Patient will go inpatient for 5 nights and after discharge from the inpatient phase will complete the 11-weeks of outpatient treatment or 2) patients who cannot complete the inpatient phase due to work or other obligations will complete the treatment 12-week study outpatient. 80 patients seeking treatment for cannabis use disorder will be enrolled into either the inpatient/outpatient or only outpatient study. This combined design will provide a comprehensive understanding of clonazepam's effects on individuals with cannabis use disorder across a range of outcome measures while also testing the medication's ability to prevent relapse in cannabis-abstinent patients.
Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Therefore, reducing the problems related to quitting cannabis may facilitate abstinence. One way to do this is by harnessing the brain's capacity to make its own cannabis-like substances - endocannabinoids. One of the main endocannabinoids is anandamide. The study is based on the hypothesis that the problems related to quitting cannabis use will be reduced by increasing the brain levels of anandamide. Furthermore, by reducing the problems related to quitting cannabis, people will be less likely to relapse. Brain anandamide levels will be increased by blocking the breakdown of anandamide using a fatty acid amide hydrolase inhibitor (FAAH-I). The effects of a novel FAAH-I cannabis withdrawal and relapse in cannabis dependent subjects will be studied in a double-blind, randomized, controlled, proof-of-concept study. Cannabis-dependent subjects will receive placebo or the FAAH-inhibitor PF-04457845 in a 2:1 randomization. The trial consists of a 1 week inpatient stay to achieve abstinence, a 3 week outpatient treatment phase. Cannabis withdrawal will be measured during the inpatient phase. Cannabis use and urinary THC-COOH levels will be measured during the entire study. The treatment phase will be followed by a safety follow up phase of 8 weeks.
Cannabis is the most widely used illicit drug in the United States, and worldwide, with 1 in 10 users estimated to meet diagnostic criteria for cannabis dependence. Avoidance of withdrawal symptoms (e.g., disturbances in mood, sleep, and craving) is a common relapse precipitant. Cannabis use also impairs executive cognitive functions thereby increasing vulnerability to relapse and reducing the ability to benefit from behavioral therapy. There are no pharmacological treatments for cannabis dependence, despite the large number of afflicted individuals and the limitations of behavioral therapies which do not remediate withdrawal and are associated with high rates of treatment failure. The primary aim of this clinical trial is to evaluate the efficacy and safety of a novel neurokinin1 (NK1) receptor antagonist, aprepitant (Emend), (125mg/day), in outpatients with current cannabis dependence. The main hypothesis to be tested is to evaluate the relative efficacy of aprepitant 125 mg/d vs. placebo for reducing cannabis withdrawal symptoms in cannabis dependent outpatients, specifically anxiety, mood, craving and sleep.
Background: Rimonabant, a CB1 receptor antagonist, blocks effects of cannabinoids and, in dependent animals, elicits cannabinoid withdrawal. No studies have examined rimonabantelicited cannabis withdrawal in humans. Goals: (1) Determine the lowest single dose of oral rimonabant that elicits measurable cannabinoid withdrawal. (2) Characterize cognitive performance, subjective state, physiological condition, and regional brain activation (measured by functional magnetic resonance imaging \[fMRI\]) during acute and chronic administration of oral delta 9-tetrahydrocannabinol (THC) and during cannabis withdrawal. (3) Characterize the pharmacokinetics of oral THC and metabolites in body fluids and hair and of rimonabant in plasma. Subject Population: Up to 60 completing cannabis users aged 18-45 (up to 24 in Experiment I, 36 in Experiment II) and 18 completing non-drug-using controls (Experiment II). Enrollment target is 82% Caucasian, 14% African American, 4% other; 9% Hispanic; 35% women. Experimental Design and Methods: Experiment I: In this within-subject, randomized, double-blind, dose-escalation study, six participants receive 7 days of THC (40-120 mg/day). On Day 8, five participants receive 20 mg rimonabant; one receives placebo. If withdrawal criteria (greater than or equal to 150% or 2.5-fold increase in selected visual-analog scales) are not met in all five participants receiving rimonabant, separate groups of six are similarly treated with 40, 60 or 80 mg rimonabant, if necessary. The PI and MRP will submit all adverse events and relevant cardiovascular and scientific data to the IRB at the completion of each rimonabant dose panel. When the extramural NIDA DSMB is in place, it will review all data collected to date and develop and implement a monitoring plan, including review on completion of each dose cohort. DSMB recommendations will be reviewed by the Sponsor, Clinical Director and IRB before proceeding to the next dose cohort. In addition, if any subject has an intolerable adverse event (ie, an adverse event leading to study discontinuation) or serious adverse event in response to rimonabant on Day 8, the blind for that subject will be broken, and a report sent to the Sponsor, the extramural NIDA DSMB when in place and the IRB for discussion. Experiment II: In this randomized, placebo-controlled, double-blind study, 36 participants receive 7 days of THC (40-120 mg/day). On Day 8, 18 participants receive rimonabant dose determined in Experiment I to elicit cannabis withdrawal; 18 participants receive placebo rimonabant to evaluate spontaneous cannabis withdrawal. Cognitive, psychological, physiological and hormonal measures are monitored to determine onset, magnitude, and duration of THC intoxication and withdrawal and to correlate with THC and rimonabant pharmacokinetics. Changes in blood oxygen level-dependent (BOLD) signal are determined with five fMRI scans throughout the study. Eighteen non-drug-using controls undergo scanning and cognitive testing at similar intervals. Risks and Benefits: The proposed doses of THC and rimonabant have been well tolerated in other studies. The most common side effects of oral THC are sedation, cognitive impairment, euphoria, poor coordination, tachycardia, and hypotension. Spontaneous withdrawal from cannabis is mild and medically benign. Experience with other drugs suggests that antagonist-elicited cannabis withdrawal may have an earlier onset and greater intensity than spontaneous cannabis withdrawal. There are no clinical benefits to participants. Scientific benefits are greater understanding of cannabis intoxication, tolerance, and withdrawal and of the role of rimonabant in eliciting cannabis withdrawal.
This treatment study is targeted specifically for those who want to stop using marijuana. We want to find out if patients who are dependent on marijuana and want to stop using are helped by a combination of the drug dronabinol and six sessions of individual therapy (BRENDA). Dronabinol is a pill form of the active ingredient in marijuana (THC). Currently, dronabinol is approved for the treatment of nausea in people receiving cancer chemotherapy and as an appetite stimulant in people with AIDS. In some studies, dronabinol reduced the amount of psychological and physical discomfort experienced when people stopped using marijuana. One purpose of our study is to see if people who are on dronabinol have fewer problems with psychological and physical discomfort than those who are on a placebo. In addition to treatment, this research trial will also be measuring the reactions of subjects to drug-related cues, and also to computer-presented tasks unrelated to drug use. We may examine whether the response to these cues/tasks either predicts treatment outcome, or is affected by your treatment. This information may also help us to understand the ways in which chronic drug use causes changes in our subjects' mental functioning and how those changes respond to treatment. In addition to participation in the treatment research trial, some subjects may be asked to undergo a brain scan in an MRI. The purpose of the brain scan research project is to measure brain reactions with a non-invasive, non-radioactive imaging technique known as fMRI (functional magnetic resonance imaging) in marijuana subjects before and after treatment with the medication dronabinol or with an inactive substance (placebo).
The purpose of this pilot study is to conduct research into the value of using the T-Break Guide for assisting people taking a tolerance break from cannabis. The hope is that this initial research will yield some insights and benchmarks into the Guide's efficacy, and provide a foundation for a later randomized control study. The following are some key research questions: 1. How did participants use the Guide? (Eg: daily; read once; 'a la carte') 2. How did using the Guide increase fidelity to tolerance break (starting, continuing, completing a break)? 3. Did using the Guide yield any benefits beyond tolerance break fidelity? (Eg: insight into patterns of use)
This is a clinical study to evaluate the efficacy of the medication gabapentin in treating persons with cannabis dependence.
The purpose of this study is to find out more about cognitive functioning in people who are cannabis dependent, relative to people who do not use cannabis, and how their brains process information after one month of not using cannabis. An additional goal is to characterize the severity of cannabis dependence using precipitated and naturalistic withdrawal with a double blind, placebo controlled, single administration of rimonabant. Research assessments occur bi-weekly throughout this 28 day study.
Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. People with schizophrenia are more likely than healthy people to abuse cannabis. Cannabis use may worsen clinical outcomes in this group, making the identification of pharmacotherapy to treat cannabis dependence in those with schizophrenia important. The investigators intend to test the combination of dronabinol, a cannabinoid agonist, and the α2-adrenergic agonist clonidine, for cannabis dependence in subjects with schizophrenia. The combination of dronabinol and clonidine may alleviate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. The investigators propose to assess the relationship of dronabinol and clonidine, when added to MM, on cannabis use patterns in cannabis-dependent patients with schizophrenia. Hypothesis: The investigators predict that combination pharmacotherapy of dronabinol and clonidine will significantly reduce cannabis use compared to those receiving placebo.
Cannabis use disorders are an important public health problem in the United States, but there are no effective medications available to treat these disorders. The investigators intend to test a medication with interesting properties, nabilone, as a treatment for cannabis dependence and to study the relationship of this treatment with the brain using functional MRI brain scans. Nabilone and marijuana have similar effects upon behaviors and the human body, suggesting that nabilone may decrease cannabis withdrawal symptoms while allowing treatment-seeking patients to benefit from behavioral treatments when they are trying to stop using cannabis. The investigators propose to assess the relationship of nabilone, when added to behavioral treatment, on cannabis use patterns in cannabis-dependent patients. The investigators also aim to determine the effects of nabilone on performance on neuropsychological tests and to assess the correlation of neuropsychological performance to brain changes using functional MRI brain scans. The investigators hypothesize that patients receiving nabilone will reduce their use of cannabis more than patients receiving placebo during this 10-week treatment trial.
The interface between cannabis use and stress is a particularly important focus for sex differences research in emerging adults. Given the dynamics at play in this critical stage when cannabis use is most prevalent, developmentally informed research is needed to guide tailored clinical interventions. This study will apply rigorous and innovative methods to elucidate sex differences in the nexus of cannabis use and stress among emerging adults with cannabis use disorder to guide the development of tailored treatments.
The primary aim of the supplemental study is to provide POC testing of aprepitant as a treatment for comorbid alcohol and cannabis dependence. The data analysis plan specified in the parent grant will likewise be applied to the supplemental project to test for effects of aprepitant vs placebo on measures of alcohol and cannabis use and protracted withdrawal. The primary hypothesis is that subjects treated with aprepitant will have significantly less alcohol and marijuana use than subjects treated with placebo.
Background: - Marijuana is the most widely used illicit drug in the world, yet relatively little is known about users who try to quit without formal treatment ( spontaneous quitting). Studies have suggested that there are some common strategies that many individuals use in spontaneous quitting, such as changing one s lifestyle or identity, reminding oneself of negative consequences, support from family and friends, and religion. However, more research is needed to determine potential treatment strategies for marijuana use. Objectives: * To identify strategies used to help with marijuana quitting among non-treatment seeking adult marijuana users. * To identify withdrawal symptoms experienced during marijuana quitting and their relationship to the quitting strategies used and the outcome of the quit attempt. * To evaluate whether subgroups of marijuana users differ in their experience of marijuana quitting. Eligibility: - Individuals at least 18 years of age who have made at least one attempt to quit marijuana use. Design: * The study will consist of one visit of approximately 1 to 2 hours. * Participants will fill out three questionnaires. The questionnaires have different types of questions, and will ask about background and lifestyle, marijuana use and craving patterns and behaviors, and difficulties in previous attempts to quit using marijuana.
The primary objective of this application is to test the neurobehavioral mechanisms and effects of aprepitant as a new cessation agent for cannabis, tobacco or both.
This is a randomized, crossover study enrolling experienced dual cannabis-tobacco smokers (N=18) to describe the differences in THC and toxicant exposure, examining pharmacokinetic, subjective, and cardiovascular effects from smoking and vaping dry herb cannabis. This study will also examine the differences in toxicant exposure and cardiovascular disease risk between smoking cannabis and smoking tobacco cigarettes.
Heavy marijuana users report experiencing trouble sleeping when they try to quit, but this has not been carefully studied. This research is being done to learn more about sleep function in heavy marijuana users, and to determine whether a medication approved for treating insomnia can help restore normal sleep function during brief periods of abstinence.