“Recreational use of marijuana is associated with few adverse effects, but abuse of synthetic cannabinoids (SCBs) can result in anxiety, psychosis, chest pain, seizures and death. To potentially explain higher toxicity associated with SCB use, we hypothesized that AB-PINACA, a common second generation SCB, exhibits atypical pharmacodynamic properties at CB1 cannabinoid receptors (CB1Rs) and/or a distinct metabolic profile when compared to Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive cannabinoid present in marijuana. Taken collectively, the atypical pharmacodynamic properties of AB-PINACA at CB1Rs relative to Δ9-THC (e.g., higher potency/efficacy and greater production of desensitization), coupled with an unusual metabolic profile (e.g., production of metabolically stable active phase I metabolites) may contribute to the pronounced adverse effects observed with abuse of this SCB compared to marijuana. ““K2” or “Spice” is a popular drug of abuse that is heavily marketed to young teens and first-time drug users as “safe” and/or “legal” marijuana”. Most K2 preparations consist of plant materials laced with a mixture of one or more SCB compounds possessing psychoactive properties similar to those produced by Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive compound found in marijuana. However, in contrast to the low incidence of adverse effects reported following use of marijuana, recreational abuse of SCBs can additionally result in anxiety, psychosis, chest pain, seizures and death. In marked contrast to K2/Spice products, marijuana contains only a single psychoactive compound Δ9-THC and a second natural constituent known as cannabidiol, that appears to blunt adverse effects produced by Δ9-THC. In fact, the beneficial combination of cannabidiol with Δ9-THC led to development of Sativex, a drug currently in clinical trials to treat a variety of indications including spasticity associated with multiple sclerosis. In addition to Δ9-THC and cannabidiol, the cannabis plant contains hundreds of other phytocannabinoids and constituents not present in K2/Spice products that may help mitigate harmful and/or adverse effects ” https://www.ncbi.nlm.nih.gov/pubmed/30319418 https://www.frontiersin.org/articles/10.3389/fphar.2018.01084/full]]>
Category Archives: Uncategorized
Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus.
“Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive.
NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1).
To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice.
These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.”
https://www.ncbi.nlm.nih.gov/pubmed/30307491
https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhy258/5126794
Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome
“Cannabis is an interesting domesticated crop with a long history of cultivation and use. Strains have been selected through informal breeding programs with undisclosed parentage and criteria. The term “strain” refers to minor morphological differences and grower branding rather than distinct cultivated varieties.
The “sativa” and “indica” lineages used to describe cannabis throughout the industry are based on postulation that sativa strains originated from European hemp cultivars, while indica are from potent, resinous Indian cannabis but given the use and trade of the plant in ancient times, the exact origin is unknown and these may not be distinct species. Comparisons of cannabinoid contents of these classifications have shown that the THC content can be identical between these two classification groups.” https://www.nature.com/articles/s41598-018-31120-2
“THC amounts identical in most cannabis strains, study finds. Newly published research from UBC’s Okanagan campus has determined that many strains of cannabis have virtually identical levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), despite their unique street names. The research shows that most strains, regardless of their origin or name, had the same amount of THC and CBD” https://phys.org/news/2018-10-thc-amounts-identical-cannabis-strains.html
“UBC Okanagan study: THC amounts identical in most cannabis strains. B.C. Kush. Platinum GSC. Blueberry Cookies. Blue Sapphire. Death Bubba. Oregon Golden Coat. Those are just some of the many, many types of marijuana available for purchase. Yet, according to newly published research from UBC Okanagan, many strains of cannabis have virtually identical levels of tetrahydrocannabinol (THC) and cannabidiol (CBD) despite their unique street names.” https://globalnews.ca/news/4533548/ubc-okanagan-study-thc-amounts-identical-in-most-cannabis-strains/
Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial.
“Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.
Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.The majority of adverse events reported during the trial were of mild or moderate severity; no serious adverse events or deaths were reported.”
https://www.ncbi.nlm.nih.gov/pubmed/30286443
https://www.epilepsybehavior.com/article/S1525-5050(18)30483-9/fulltext]]>A systematic review on the neuroprotective perspectives of beta-caryophyllene.
“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.
This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.
A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.
Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”
https://www.ncbi.nlm.nih.gov/pubmed/30281175
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“A comparative study of