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International Journal of Molecular... Mar 2022Medical case reports suggest that cannabinoids extracted from have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of... (Review)
Review
Medical case reports suggest that cannabinoids extracted from have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of its major component, Δ9-tetrahydrocannabinol (THC). The new scientific discoveries related to the endocannabinoid system, including new receptors, ligands, and mediators, allowed the development of new therapeutic targets for the treatment of several pathological disorders minimizing the undesirable psychotropic effects of some constituents of this plant. Today, FDA-approved drugs, such as nabiximols (a mixture of THC and non-psychoactive cannabidiol (CBD)), are employed in alleviating pain and spasticity in multiple sclerosis. Dronabinol and nabilone are used for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Dronabinol was approved for the treatment of anorexia in patients with AIDS (acquired immune deficiency syndrome). In this review, we highlighted the potential therapeutic efficacy of natural and synthetic cannabinoids and their clinical relevance in cancer, neurodegenerative and dermatological diseases, and viral infections.
Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Endocannabinoids; Humans; Neoplasms
PubMed: 35328765
DOI: 10.3390/ijms23063344 -
British Journal of Clinical Pharmacology Nov 2018There is increasing interest in the use of cannabinoids for disease and symptom management, but limited information available regarding their pharmacokinetics and... (Review)
Review
There is increasing interest in the use of cannabinoids for disease and symptom management, but limited information available regarding their pharmacokinetics and pharmacodynamics to guide prescribers. Cannabis medicines contain a wide variety of chemical compounds, including the cannabinoids delta-9-tetrahydrocannabinol (THC), which is psychoactive, and the nonpsychoactive cannabidiol (CBD). Cannabis use is associated with both pathological and behavioural toxicity and, accordingly, is contraindicated in the context of significant psychiatric, cardiovascular, renal or hepatic illness. The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements. As both THC and CBD are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters. An important example is the CBD-mediated inhibition of clobazam metabolism. Pharmacodynamic interactions may occur if cannabis is administered with other central nervous system depressant drugs, and cardiac toxicity may occur via additive hypertension and tachycardia with sympathomimetic agents. More vulnerable populations, such as older patients, may benefit from the potential symptomatic and palliative benefits of cannabinoids but are at increased risk of adverse effects. The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects. Further clinical studies in the actual patient populations for whom prescribing may be considered are needed, to derive a better understanding of these drugs and enhance safe and optimal prescribing.
Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Interactions; Humans
PubMed: 30001569
DOI: 10.1111/bcp.13710 -
Nature Reviews. Neuroscience Jul 2021Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended... (Review)
Review
Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended neurodevelopmental implications given the increased use of cannabis and the potent levels of Δ-tetrahydrocannabinol today being consumed by pregnant women, young mothers and teens. In this Review, we provide an overview of the neurobiological effects of cannabinoid exposure during prenatal/perinatal and adolescent periods, in which the endogenous cannabinoid system plays a fundamental role in neurodevelopmental processes. We highlight impaired synaptic plasticity as characteristic of developmental exposure and the important contribution of epigenetic reprogramming that maintains the long-term impact into adulthood and across generations. Such epigenetic influence by its very nature being highly responsive to the environment also provides the potential to diminish neural perturbations associated with developmental cannabis exposure.
Topics: Adolescent; Adult; Age Factors; Animals; Brain; Cannabis; Child; Child, Preschool; Dronabinol; Endocannabinoids; Epigenesis, Genetic; Female; Humans; Infant; Lactation; Lipase; Male; Marijuana Smoking; Maternal Exposure; Mice; Milk, Human; Neurodevelopmental Disorders; Neuronal Plasticity; Neurotransmitter Agents; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Receptor, Cannabinoid, CB1; Species Specificity; Young Adult
PubMed: 34021274
DOI: 10.1038/s41583-021-00465-5 -
Sports Medicine (Auckland, N.Z.) Sep 2021Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for... (Review)
Review
Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes' performance and recovery.
Topics: Athletic Performance; Cannabidiol; Cannabis; Dronabinol; Humans; Pain
PubMed: 34515970
DOI: 10.1007/s40279-021-01505-x -
Drug and Alcohol Dependence Nov 2014Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine... (Review)
Review
BACKGROUND
Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests.
METHODS
We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications.
Topics: Animals; Cannabinoids; Designer Drugs; Dronabinol; Humans; Protein Binding; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2
PubMed: 25220897
DOI: 10.1016/j.drugalcdep.2014.08.005 -
Proceedings of the National Academy of... Mar 2020With the growing global acceptance of cannabis and its widespread use by eyewitnesses and suspects in legal cases, understanding the popular drug's ramifications for... (Randomized Controlled Trial)
Randomized Controlled Trial
With the growing global acceptance of cannabis and its widespread use by eyewitnesses and suspects in legal cases, understanding the popular drug's ramifications for memory is a pressing need. In a double-blind, randomized, placebo-controlled trial, we examined the acute and delayed effects of Δ9-tetrahydrocannabinol (THC) intoxication on susceptibility to false memory in 64 healthy volunteers. Memory was tested immediately (encoding and retrieval under drug influence) and 1 wk later (retrieval sober). We used three different methods (associative word lists and two misinformation tasks using virtual reality). Across all methods, we found evidence for enhanced false-memory effects in intoxicated participants. Specifically, intoxicated participants showed higher false recognition in the associative word-list task both at immediate and delayed test than controls. This yes bias became increasingly strong with decreasing levels of association between studied and test items. In a misinformation task, intoxicated participants were more susceptible to false-memory creation using a virtual-reality eyewitness scenario and virtual-reality perpetrator scenario. False-memory effects were mostly restricted to the acute-intoxication phase. Cannabis seems to increase false-memory proneness, with decreasing strength of association between an event and a test item, as assessed by different false-memory paradigms. Our findings have implications for how and when the police should interview suspects and eyewitnesses.
Topics: Communication; Dronabinol; Female; Humans; Male; Memory; Repression, Psychology; Young Adult
PubMed: 32041881
DOI: 10.1073/pnas.1920162117 -
British Journal of Pharmacology Aug 2011Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic... (Review)
Review
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL(-1) . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. http://dx.doi.org/10.1111/bph.2011.163.issue-7.
Topics: Animals; Cannabis; Dronabinol; Drug Synergism; Humans; Phytotherapy; Terpenes
PubMed: 21749363
DOI: 10.1111/j.1476-5381.2011.01238.x -
British Journal of Pharmacology Aug 2022The use of the intoxicating cannabinoid delta-8-tetrahydrocannabinol (Δ -THC) has grown rapidly over the last several years. There have been dozens of Δ -THC studies... (Review)
Review
The use of the intoxicating cannabinoid delta-8-tetrahydrocannabinol (Δ -THC) has grown rapidly over the last several years. There have been dozens of Δ -THC studies dating back over many decades, yet no review articles have comprehensively covered these findings. In this review, we summarize the pharmacological studies of Δ -THC, including receptor binding, cell signalling, in vivo cannabimimetic activity, clinical activity and pharmacokinetics. We give special focus to studies that directly compared Δ -THC to its more commonly studied isomer, Δ -THC. Overall, the pharmacokinetics and pharmacodynamics of Δ -THC and Δ -THC are very similar. Δ -THC is a partial agonist of the cannabinoid CB receptor and has cannabimimetic activity in both animals and humans. The reduced potency of Δ -THC in clinical studies compared with Δ -THC can be explained by weaker cannabinoid CB receptor affinity, although there are other plausible mechanisms that may contribute. We highlight the gaps in our knowledge of Δ -THC pharmacology where further studies are needed, particularly in humans.
Topics: Animals; Cannabinoids; Dronabinol; Humans; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid
PubMed: 35523678
DOI: 10.1111/bph.15865 -
Australian Journal of General Practice Aug 2022Anxiety is second most common reason for medicinal cannabis prescription in Australia and is being treated with both Δ9-tetrahydrocannabinol (THC)-containing...
BACKGROUND
Anxiety is second most common reason for medicinal cannabis prescription in Australia and is being treated with both Δ9-tetrahydrocannabinol (THC)-containing and cannabidiol (CBD)-dominant products.
OBJECTIVE
The aim of this article is to summarise recent advances in the understanding of medicinal cannabis in treating anxiety and recent trends in prescribing.
DISCUSSION
Clinical trials and laboratory studies provide evidence of anxiolytic effects of CBD in healthy volunteers and clinical populations, although current evidence is insufficient to support CBD as a first-line treatment. The evidence regarding the use of THC-dominant products for anxiety is ambiguous, with exacerbation of anxiety in some individuals and relief in others. Caution is required as THC can impair driving and cognitive function. Despite the lack of robust supportive evidence, prescription of medicinal cannabis products for anxiety is increasing rapidly, while illicit cannabis is widely used in the community to self-medicate anxiety. Approximately 17% of current prescriptions for anxiety are for CBD- dominant liquid products (oils), wafers and capsules, while the remainder are for THC-containing liquid products (33%) and herbal cannabis for vaporisation (50%). Medical practitioners should carefully consider potential risks and benefits when prescribing medicinal cannabis for anxiety disorders and should 'start low and go slow'.
Topics: Analgesics; Anxiety Disorders; Cannabidiol; Cannabis; Dronabinol; Humans; Medical Marijuana
PubMed: 35908759
DOI: 10.31128/AJGP-04-21-5936 -
JAMA Dec 2020Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear.
OBJECTIVE
To determine the driving impairment caused by vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) and CBD.
DESIGN, SETTING, AND PARTICIPANTS
A double-blind, within-participants, randomized clinical trial was conducted at the Faculty of Psychology and Neuroscience at Maastricht University in the Netherlands between May 20, 2019, and March 27, 2020. Participants (N = 26) were healthy occasional users of cannabis.
INTERVENTIONS
Participants vaporized THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis. THC and CBD doses were 13.75 mg. Order of conditions was randomized and balanced.
MAIN OUTCOMES AND MEASURES
The primary end point was standard deviation of lateral position (SDLP; a measure of lane weaving) during 100 km, on-road driving tests that commenced at 40 minutes and 240 minutes after cannabis consumption. At a calibrated blood alcohol concentration (BAC) of 0.02%, SDLP was increased relative to placebo by 1.12 cm, and at a calibrated BAC of 0.05%, SDLP was increased relative to placebo by 2.4 cm.
RESULTS
Among 26 randomized participants (mean [SD] age, 23.2 [2.6] years; 16 women), 22 (85%) completed all 8 driving tests. At 40 to 100 minutes following consumption, the SDLP was 18.21 cm with CBD-dominant cannabis, 20.59 cm with THC-dominant cannabis, 21.09 cm with THC/CBD-equivalent cannabis, and 18.28 cm with placebo cannabis. SDLP was significantly increased by THC-dominant cannabis (+2.33 cm [95% CI, 0.80 to 3.86]; P < .001) and THC/CBD-equivalent cannabis (+2.83 cm [95% CI, 1.28 to 4.39]; P < .001) but not CBD-dominant cannabis (-0.05 cm [95% CI, -1.49 to 1.39]; P > .99), relative to placebo. At 240 to 300 minutes following consumption, the SDLP was 19.03 cm with CBD-dominant cannabis, 19.88 cm with THC-dominant cannabis, 20.59 cm with THC/CBD-equivalent cannabis, and 19.37 cm with placebo cannabis. The SDLP did not differ significantly in the CBD (-0.34 cm [95% CI, -1.77 to 1.10]; P > .99), THC (0.51 cm [95% CI, -1.01 to 2.02]; P > .99) or THC/CBD (1.22 cm [95% CI, -0.29 to 2.72]; P = .20) conditions, relative to placebo. Out of 188 test drives, 16 (8.5%) were terminated due to safety concerns.
CONCLUSIONS AND RELEVANCE
In a crossover clinical trial that assessed driving performance during on-road driving tests, the SDLP following vaporized THC-dominant and THC/CBD-equivalent cannabis compared with placebo was significantly greater at 40 to 100 minutes but not 240 to 300 minutes after vaporization; there were no significant differences between CBD-dominant cannabis and placebo. However, the effect size for CBD-dominant cannabis may not have excluded clinically important impairment, and the doses tested may not represent common usage.
TRIAL REGISTRATION
EU Clinical Trials Register: 2018-003945-40.
Topics: Adult; Automobile Driver Examination; Cannabidiol; Cognition; Cross-Over Studies; Double-Blind Method; Driving Under the Influence; Dronabinol; Female; Healthy Volunteers; Humans; Male; Psychomotor Performance; Vaping; Young Adult
PubMed: 33258890
DOI: 10.1001/jama.2020.21218