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Addiction Biology Sep 2013Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid... (Randomized Controlled Trial)
Randomized Controlled Trial
Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.
Topics: Adult; Affect; Analysis of Variance; Biological Availability; Blood Pressure; Cannabinoid Receptor Agonists; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Heart Rate; Humans; Male; Marijuana Abuse; Middle Aged; Placebos; Psychomotor Performance; Secondary Prevention; Substance Withdrawal Syndrome; Time Factors; Young Adult
PubMed: 22260337
DOI: 10.1111/j.1369-1600.2011.00427.x -
Journal of Psychiatric Practice Sep 2014With 23 states and the District of Columbia having enacted medical marijuana laws as of August 2014, it is important that psychiatrists be able to address questions... (Review)
Review
With 23 states and the District of Columbia having enacted medical marijuana laws as of August 2014, it is important that psychiatrists be able to address questions about medical marijuana from patients, families, and other health care professionals. The author discusses the medical literature on synthetic cannabinoids and medical marijuana. The synthetic cannabinoids dronabinol and nabilone are approved by the United States Food and Drug Administration for nausea and vomiting associated with cancer chemotherapy and appetite stimulation in patients with wasting diseases such as acquired immunodeficiency syndrome (AIDS). Results of clinical trials of these agents for other conditions have varied widely thus far. In addition, few data are available on the use of the marijuana plant as a medical treatment. The author concludes that there is a clear need for additional research on possible medical uses of cannabinoids. He notes that discussions with prospective medical marijuana patients should emphasize the importance of communication among all parties due to the possible side effects of treatment with marijuana and its potential to interact with other medications the patient may be taking. Facilitating a thorough substance abuse consultation is one of most positive ways that psychiatrists, especially addiction psychiatrists, can make an impact as medical marijuana becomes increasingly common. A careful review of the prospective medical marijuana user's substance use history, co-occurring medical and psychiatric conditions, family history, and psychosocial stressors is essential in evaluating the potential risks of medical marijuana for these patients. The author concludes that psychiatrists can have a significant impact by increasing the likelihood that medical marijuana will be used in a safe and responsible way.
Topics: Antiemetics; District of Columbia; Dronabinol; Humans; Medical Marijuana; Nausea; Psychiatry; United States; Vomiting; Wasting Syndrome
PubMed: 25226202
DOI: 10.1097/01.pra.0000454786.97976.96 -
Molecules (Basel, Switzerland) Oct 2022Due to increased concerns regarding unidentified impurities in delta-8 tetrahydrocannabinol (Δ-8 THC) consumer products, a study using Nuclear Magnetic Resonance (NMR),...
Due to increased concerns regarding unidentified impurities in delta-8 tetrahydrocannabinol (Δ-8 THC) consumer products, a study using Nuclear Magnetic Resonance (NMR), high performance liquid chromatography (HPLC), and mass spectrometry (MS) was conducted to further investigate these products. Ten Δ-8 THC products, including distillates and ready to use vaporizer cartridges, were analyzed. The results yield findings that the tested products contain several impurities in concentrations far beyond what is declared on certificates of analysis for these products. As Δ-8 THC is a synthetic product synthesized from cannabidiol (CBD), there are valid concerns regarding the presence of impurities in these products with unknown effects on the human body. Compounding this problem is apparent inadequate testing of these products by producers and independent laboratories.
Topics: Humans; Cannabidiol; Dronabinol; Cannabis; Chromatography, High Pressure Liquid; Magnetic Resonance Imaging
PubMed: 36296514
DOI: 10.3390/molecules27206924 -
Pharmacology Research & Perspectives Apr 2018Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2... (Review)
Review
Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases. It may be considered to be a disease-modifying drug unlike most NSAIDs that only provide symptomatic relief. AJA is currently being evaluated in 24-month open-label extension studies in SSc and in skin-predominant DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has recently been initiated.
Topics: Animals; Chronic Disease; Clinical Trials as Topic; Dronabinol; Drug Evaluation, Preclinical; Humans; Inflammation; Treatment Outcome
PubMed: 29638269
DOI: 10.1002/prp2.394 -
International Journal of Molecular... Apr 2023Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp...
Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood-brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer's disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aβ-treated mouse model. We observed that Aβ-treated mice had more hippocampal Aβ and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. However, CBDA- and THCA-treated mice showed decreased hippocampal Aβ and p-tau and superior cognitive function compared with Aβ-treated mice. In addition, CBDA and THCA lowered Aβ and p-tau levels, alleviated calcium dyshomeostasis, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca, Aβ, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD.
Topics: Mice; Animals; Dronabinol; Alzheimer Disease; Neuroprotective Agents; Cannabinoids; Cannabidiol; Cannabis; Amyloid beta-Peptides; Memory Disorders
PubMed: 37047798
DOI: 10.3390/ijms24076827 -
Yakugaku Zasshi : Journal of the... 2020Cannabis use among the younger population in Japan has been steadily increasing. The aim of the present review is to highlight recent knowledge regarding the molecular... (Review)
Review
Cannabis use among the younger population in Japan has been steadily increasing. The aim of the present review is to highlight recent knowledge regarding the molecular mechanisms of action and health risks associated with cannabis and synthetic cannabinoid consumption. We investigated the effects of Δ-tetrahydrocannabinol (THC) and synthetic cannabinoids on place conditioning in ICR mice. Both Δ-THC and synthetic cannabinoids produce a significant conditioned place preference. These rewarding effects were completely suppressed by the cannabinoid CB receptor type antagonist AM251. The cytotoxicological effects of Δ-THC and synthetic cannabinoids were also characterized in the limbic forebrain of mice in primary culture in vitro. Δ-THC and synthetic cannabinoids caused cell death in a dose-dependent manner. The rank order of cytotoxicological potency was synthetic cannabinoids>Δ-THC and related to the agonistic activities of the CB receptor. A recent review on the harmful effects of cannabis use in humans reported that behavioral impairments, especially in terms of attention, memory, and complex information-processing ability, can last for many weeks after cessation of cannabis use among heavy users. In addition, cannabis use could be a risk factor for drug dependence and later psychosis among adolescents. The results of animal and human studies suggest that CB receptors play an important role in the expression of harmful effects of cannabis and synthetic cannabinoid use. Moreover, concern regarding increasing concentrations of Δ-THC in cannabis in many countries has been noted, because more potent cannabis may be associated with worse adverse effects.
Topics: Animals; Cannabis; Cell Death; Dose-Response Relationship, Drug; Dronabinol; Humans; Receptor, Cannabinoid, CB1; Substance-Related Disorders
PubMed: 32009044
DOI: 10.1248/yakushi.19-00195-4 -
Journal of Natural Products Sep 2021The -stereoisomers of Δ-THC [(-)- and (+)-] were identified and quantified in a series of low-THC-containing varieties of registered in Europe as fiber hemp and in...
The -stereoisomers of Δ-THC [(-)- and (+)-] were identified and quantified in a series of low-THC-containing varieties of registered in Europe as fiber hemp and in research accessions of cannabis. While Δ--THC () occurs in cannabis fiber hemp in the concentration range of (-)-Δ--THC [(-)-], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ--THC () is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6a,10a [(-)-] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (-)-Δ--THC [(-)-], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of "Δ-THC and isomers" and needs therefore revision, or at least a more specific wording, to account for the presence of Δ--THCs [(+)- and (-)-] in cannabis fiber hemp varieties.
Topics: Animals; Cannabinoids; Cannabis; Dronabinol; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Stereoisomerism
PubMed: 34304557
DOI: 10.1021/acs.jnatprod.1c00513 -
Pharmacology & Therapeutics Feb 2018The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with... (Review)
Review
The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with cannabis use, particularly for sensitive subgroups such as pregnant women, are difficult to define because of a paucity of dose-response data and the recent increase in cannabis potency. Although there is a large body of evidence detailing the mode of action of Δ-tetrahydrocannabinol (THC) in adults, little work has focused on understanding how cannabis use during pregnancy may impact the development of the fetal nervous system and whether additional plant-derived cannabinoids might participate. This manuscript presents an overview of the historical and contemporary literature focused on the mode of action of THC in the developing brain, comparative pharmacokinetics in both pregnant and nonpregnant model systems and neurodevelopmental outcomes in exposed offspring. Despite growing public health significance, pharmacokinetic studies of THC have focused on nonpregnant adult subjects and there are few published reports on disposition parameters during pregnancy. Data from preclinical species show that THC readily crosses the placenta although fetal exposures appear lower than maternal exposures. The neurodevelopmental data in humans and animals suggest that prenatal exposure to THC may lead to subtle, persistent changes in targeted aspects of higher-level cognition and psychological well-being. There is an urgent need for well-controlled studies in humans and preclinical models on THC as a developmental neurotoxicant. Until more information is available, pregnant women should not assume that using cannabis during pregnancy is safe.
Topics: Animals; Brain; Cognition; Dronabinol; Female; Humans; Marijuana Use; Models, Neurological; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28847562
DOI: 10.1016/j.pharmthera.2017.08.014 -
Medicina (Kaunas, Lithuania) May 2020Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient... (Review)
Review
Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic potential of cannabis and paved the way for the release of marketing authorizations for cannabis-based products. Although several synthetic and standardized products are currently available on the market, patients' preferences lean towards herbal preparations, because they are easy to handle and self-administer. A literature search was conducted on multidisciplinary research databases and international agencies or institutional websites. Despite the growing popularity of medical cannabis, little data is available on the chemical composition and preparation methods of medical cannabis extracts. The authors hereby report the most common cannabis preparations, presenting their medical indications, routes of administration and recommended dosages. A practical and helpful guide for prescribing doctors is provided, including suggested posology, titration strategies and cannabinoid amounts in herbal preparations obtained from different sources of medical cannabis.
Topics: Cannabidiol; Dronabinol; Herbal Medicine; Humans; Medical Marijuana; Plant Preparations
PubMed: 32429074
DOI: 10.3390/medicina56050237 -
Forensic Science International Dec 2016Passive exposure to cannabis smoke may induce effects on behavior and psychomotor skills, and have legal consequences, including the risk of being falsely considered as... (Review)
Review
Passive exposure to cannabis smoke may induce effects on behavior and psychomotor skills, and have legal consequences, including the risk of being falsely considered as a cannabis user. This can become a concern, especially in occupational contexts or when driving vehicles. In order to enable a differentiation between a passive and an active exposure to cannabis and to limit the likeliness to be detected positive following passive exposure, this review identified specific biomarkers of passive exposure in urine, blood, oral fluid, hair, and sebum. Out of 958 papers identified on passive exposure to cannabis, 21 were selected. Although positive tests had been observed in all matrices following extremely high passive exposure, some distinctive features were observed in each matrix compared to cannabis active use. More specifically, in everyday life conditions, 11-nor-delta-9-THC-carboxylic acid (THC-COOH) urinary level should be detected below the positivity threshold used to confirm active smoking of cannabis, especially after normalization to creatinine level. Measuring delta-9-tetrahydrocannabinol (THC) and THC-COOH in blood is an appropriate alternative for appraising passive exposure as low and very low concentrations of THC and THC-COOH, respectively, should be measured. In hair, oral fluid (OF) and sweat/sebum emulsion, no THCCOOH should be detected. Its presence in hair argues for regular cannabis consumption and in OF or sweat for recent consumption. The experts should recommend to persons who have to demonstrate abstinence from cannabis to avoid heavily smoky and unventilated environments.
Topics: Biomarkers; Dronabinol; Hair; Humans; Marijuana Smoking; Saliva; Sweat; Tobacco Smoke Pollution
PubMed: 27883985
DOI: 10.1016/j.forsciint.2016.11.017