-
International Journal of Molecular... Sep 2023Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have... (Review)
Review
Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.
Topics: Humans; Cannabis; Endocannabinoids; Cannabinoids; Cannabinoid Receptor Agonists; Gastrointestinal Diseases; Hallucinogens; Drug Development; Dronabinol
PubMed: 37834122
DOI: 10.3390/ijms241914677 -
International Journal of Obesity (2005) Apr 2019
Topics: Appetite Stimulants; Dronabinol; Humans; Medical Marijuana; Obesity
PubMed: 30755697
DOI: 10.1038/s41366-019-0334-z -
Neuropsychopharmacology : Official... Oct 2023The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this... (Randomized Controlled Trial)
Randomized Controlled Trial
The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.
Topics: Humans; Adult; Female; Middle Aged; Male; Analgesics, Opioid; Hydromorphone; Chronic Pain; Cannabinoids; Dronabinol; Osteoarthritis, Knee; Analgesics; Double-Blind Method
PubMed: 37202479
DOI: 10.1038/s41386-023-01597-1 -
Behavioural Pharmacology Apr 2022Cannabis is one of the most frequently used psychoactive substances in the world. The most common route of administration for cannabis and cannabinoid constituents such... (Review)
Review
Cannabis is one of the most frequently used psychoactive substances in the world. The most common route of administration for cannabis and cannabinoid constituents such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is via smoking or vapor inhalation. Preclinical vapor models have been developed, although the vaporization devices and delivery methods vary widely across laboratories. This review examines the emerging field of preclinical vapor models with a focus on cannabinoid exposure in order to (1) summarize vapor exposure parameters and other methodological details across studies; (2) discuss the pharmacological and behavioral effects produced by exposure to vaporized cannabinoids; and (3) compare behavioral effects of cannabinoid vapor administration with those of other routes of administration. This review will serve as a guide for past and current vapor delivery methods in animals, synergize findings across studies, and propose future directions for this area of research.
Topics: Animals; Animals, Laboratory; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Dronabinol; Hallucinogens
PubMed: 33136615
DOI: 10.1097/FBP.0000000000000592 -
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 -
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 -
Deutsches Arzteblatt International Dec 2023Cannabinoid drugs containing tetrahydrocannabinol (THC), or its structural analogues, as monotherapeutic agents or as extracts or botanical preparations with or without... (Review)
Review
BACKGROUND
Cannabinoid drugs containing tetrahydrocannabinol (THC), or its structural analogues, as monotherapeutic agents or as extracts or botanical preparations with or without cannabidiol (CBD) are often prescribed to multimorbid patients who are taking multiple drugs. This raises the question of the risk of drug interactions.
METHODS
This review of the pharmacokinetics and pharmacodynamics of interactions with cannabinoid drugs and their potential effects is based on pertinent publications retrieved by a selective literature search.
RESULTS
As THC and CBD are largely metabolized in the liver, their bioavailability after oral or oral-mucosal administration is low (6-8% and 11-13%, respectively). The plasma concentrations of THC and its active metabolite 11-OH-THC can be increased by strong CYP3A4 inhibitors (verapamil, clarithromycin) and decreased by strong CYP3A4 inductors (rifampicin, carbamazepine). The clinical significance of these effects is unclear because of the variable plasma level and therapeutic spectrum of THC. The metabolism of CBD is less dependent on cytochrome P450 enzymes than that of THC. THC and CBD inhibit CYP2C and CYP3A4; the corresponding clinically relevant drug interactions probably are likely to arise only with THC doses above 30 mg/day and CBD doses above 300 mg/day.
CONCLUSION
Potential drug interactions with THC and CBD are probably of little importance at low or moderate doses. Strong CYP inhibitors or inductors can intensify or weaken their effect. Slowly ramping up the dose of oral cannabinoid drugs can lessen their pharmacodynamic interactions, which can generally be well controlled. Administration by inhalation can worsen the interactions.
Topics: Humans; Cannabinoids; Cannabidiol; Dronabinol; Pharmaceutical Preparations; Cytochrome P-450 CYP3A; Drug Interactions
PubMed: 37874128
DOI: 10.3238/arztebl.m2023.0223 -
Cell Metabolism Jul 2023One of cannabis' most iconic effects is the stimulation of hedonic high-calorie eating-the "munchies"-yet habitual cannabis users are, on average, leaner than non-users....
One of cannabis' most iconic effects is the stimulation of hedonic high-calorie eating-the "munchies"-yet habitual cannabis users are, on average, leaner than non-users. We asked whether this phenotype might result from lasting changes in energy balance established during adolescence, when use of the drug often begins. We found that daily low-dose administration of cannabis' intoxicating constituent, Δ-tetrahydrocannabinol (THC), to adolescent male mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, enhanced thermogenesis, and impaired cold- and β-adrenergic receptor-stimulated lipolysis. Further analyses revealed that this phenotype is associated with molecular anomalies in the adipose organ, including ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring "pseudo-lean" state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.
Topics: Mice; Male; Animals; Dronabinol; Obesity; Adiposity; Energy Intake; Homeostasis
PubMed: 37267956
DOI: 10.1016/j.cmet.2023.05.002 -
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 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