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The New England Journal of Medicine Dec 2023
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Pharmacological Reviews Sep 2023The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the... (Review)
Review
The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research evidence and the Food and Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ-tetrahydrocannabinol and other plant-derived cannabinoids (phytocannabinoids). Of note, our body has a complex endocannabinoid system (ECS)made of receptors, metabolic enzymes, and transportersthat is also regulated by phytocannabinoids. The first endocannabinoid to be discovered 30 years ago was anandamide (-arachidonoyl-ethanolamine); since then, distinct elements of the ECS have been the target of drug design programs aimed at curing (or at least slowing down) a number of human diseases, both in the central nervous system and at the periphery. Here a critical review of our knowledge of the goods and bads of the ECS as a therapeutic target is presented to define the benefits of ECS-active phytocannabinoids and ECS-oriented synthetic drugs for human health. SIGNIFICANCE STATEMENT: The endocannabinoid system plays important roles virtually everywhere in our body and is either involved in mediating key processes of central and peripheral diseases or represents a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of the components of this complex system, and in particular of key receptors (like cannabinoid receptors 1 and 2) and metabolic enzymes (like fatty acid amide hydrolase and monoacylglycerol lipase), will advance our understanding of endocannabinoid signaling and activity at molecular, cellular, and system levels, providing new opportunities to treat patients.
Topics: Humans; Child; Endocannabinoids; Cannabidiol; Cannabinoids; Dronabinol; Cannabis; Carrier Proteins; Hallucinogens; Cannabinoid Receptor Agonists
PubMed: 37164640
DOI: 10.1124/pharmrev.122.000600 -
Drug Testing and Analysis Feb 2024Since the early 2000s, there has been a turmoil on the global illicit cannabinoid market. Parallel to legislative changes in some jurisdictions regarding herbal... (Review)
Review
Since the early 2000s, there has been a turmoil on the global illicit cannabinoid market. Parallel to legislative changes in some jurisdictions regarding herbal cannabis, unregulated and cheap synthetic cannabinoids with astonishing structural diversity have emerged. Recently, semi-synthetic cannabinoids manufactured from hemp extracts by simple chemical transformations have also appeared as recreational drugs. The burst of these semi-synthetic cannabinoids into the market was sparked by legislative changes in the United States, where cultivation of industrial hemp restarted. By now, hemp-derived cannabidiol (CBD), initially a blockbuster product on its own, became a "precursor" to semi-synthetic cannabinoids such as hexahydrocannabinol (HHC), which appeared on the drug market in 2021. The synthesis and cannabimimetic activity of HHC were first reported eight decades ago in quest for the psychoactive principles of marijuana and hashish. Current large-scale manufacture of HHC is based on hemp-derived CBD extract, which is converted first by cyclization into a Δ /Δ -THC mixture, followed by catalytic hydrogenation to afford a mixture of (9R)-HHC and (9S)-HHC epimers. Preclinical studies indicate that (9R)-HHC has THC-like pharmacological properties. The animal metabolism of HHC is partially clarified. The human pharmacology including metabolism of HHC is yet to be investigated, and (immuno)analytical methods for the rapid detection of HHC or its metabolites in urine are lacking. Herein, the legal background for the revitalization of hemp cultivation, and available information on the chemistry, analysis, and pharmacology of HHC and related analogs, including HHC acetate (HHC-O) is reviewed.
Topics: Animals; Humans; United States; Cannabinoids; Cannabis; Cannabidiol; Cannabinoid Receptor Agonists; Illicit Drugs; Hallucinogens; Dronabinol
PubMed: 37269160
DOI: 10.1002/dta.3519 -
The Psychiatric Clinics of North America Dec 2023Psychosis and cannabis use may overlap in multiple ways in young people. Research suggests that cannabis use increases risk for having psychotic symptoms, both... (Review)
Review
Psychosis and cannabis use may overlap in multiple ways in young people. Research suggests that cannabis use increases risk for having psychotic symptoms, both attenuated (subthreshold) and acute. Cannabis use may also exacerbate psychosis symptoms among young people with underlying psychosis risk and psychotic disorders. Although there are suggestions for treating co-occurring psychosis and cannabis use in young people (e.g., incorporating cannabis use assessment and treatment strategies into specialized early psychosis care), there are many gaps in clinical trial research to support evidence-based treatment of these overlapping concerns.
Topics: Humans; Adolescent; Cannabis; Psychotic Disorders
PubMed: 37879833
DOI: 10.1016/j.psc.2023.03.006 -
Cannabis and Cannabinoid Research Apr 2024Hexahydrocannabinols (HHCs), referred to as (9)-HHC and (9)-HHC diastereoisomers, are poorly studied cannabinoids naturally found in small concentrations in the pollen...
Hexahydrocannabinols (HHCs), referred to as (9)-HHC and (9)-HHC diastereoisomers, are poorly studied cannabinoids naturally found in small concentrations in the pollen and the seeds of the hemp plants. In this study, for the first time, we describe the finding of (9)-HHC and (9)-HHC in two commercialized hemp derived products. The achievement of reference standards by semisynthetic or isolation approach allows us to develop and validate a gas chromatography mass spectrometry method for the identification and quantification of HHCs in hemp-derived resin. The two analyzed samples showed percentage of 42.5 and 41.5 for (9)-HHC and of 23.6 and 23.6 for (9)-HHC. Despite the lack of in-depth studies about HHCs activity, potency, toxicity, and safety, these cannabinoids are emerging on the light-cannabis (hemp) market probably because legislations still do not clearly regulate them. Since analytical assay for hemp-derived products usually include only Δ-THC, THC-A, CBD, and CBD-A, a thorough investigation could be carried out to reveal the possible addition of "new" compounds that might be a matter of safety.
Topics: Cannabis; Cannabinoids; Hallucinogens; Cannabinoid Receptor Agonists; Gas Chromatography-Mass Spectrometry
PubMed: 36445181
DOI: 10.1089/can.2022.0253 -
Science (New York, N.Y.) Sep 2023As states relax their laws on cannabis, neuroscientist Yasmin Hurd is warning about the drug's dangers for the developing brain.
As states relax their laws on cannabis, neuroscientist Yasmin Hurd is warning about the drug's dangers for the developing brain.
Topics: Child; Female; Humans; Pregnancy; Brain; Cannabis; Child Development; Dronabinol; Psychotropic Drugs; Pregnant Women; Marijuana Smoking
PubMed: 37651516
DOI: 10.1126/science.adk5505 -
MMW Fortschritte Der Medizin Oct 2023
Topics: Humans; Cannabis; Psychotic Disorders
PubMed: 37828304
DOI: 10.1007/s15006-023-3032-7 -
Zeitschrift Fur Kinder- Und... Sep 2023
Topics: Humans; Cannabis; Marijuana Use
PubMed: 37681652
DOI: 10.1024/1422-4917/a000945 -
The American Journal of Nursing May 2024Care for those seeking guidance in the therapeutic use of cannabis.
Care for those seeking guidance in the therapeutic use of cannabis.
Topics: Humans; Medical Marijuana; Cannabis
PubMed: 38661699
DOI: 10.1097/01.NAJ.0001016368.03202.a8 -
The Psychiatric Clinics of North America Dec 2023With increasing cannabis potency, increasing variety of methods of cannabis use, and lower perceived risk of cannabis use, it is increasingly important clinicians who... (Review)
Review
With increasing cannabis potency, increasing variety of methods of cannabis use, and lower perceived risk of cannabis use, it is increasingly important clinicians who work with adolescents remain up-to-date on the latest literature regarding cannabis use and its associated outcomes. Adolescent cannabis use is associated with chronic cognitive, psychosocial, psychiatric, and physical outcomes. Clinicians working in this field should be able to recognize cannabis use disorder, understand how adolescent cannabis use can impact the developing mind, and have informed discussions with patients and families regarding risks of use.
Topics: Humans; Adolescent; Marijuana Abuse; Substance-Related Disorders; Cannabis
PubMed: 37879829
DOI: 10.1016/j.psc.2023.03.013