“Research interest has grown around the potential therapeutic use of cannabidiol in mood-related disorders, due to its anxiolytic and antidepressant-like effects.
These have been partially attributed to its action as an allosteric modulator of 5-HTR1A. However, the exact mechanism supporting cannabidiol properties remains unclear.
“Cannabis sativa L. is a dioecious plant belonging to the Cannabaceae family. The main phytochemicals that are found in this plant are represented by cannabinoids, flavones, and terpenes. Some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to a synergistic action.
In the light of all the above, the present study was aimed at the multi-component analysis of the bioactive compounds present in fibre-type C. sativa (hemp) inflorescences of different varieties by means of innovative HPLC and GC methods. In particular, the profiling of non-psychoactive cannabinoids was carried out by means of HPLC-UV/DAD, ESI-MS, and MS². The content of prenylated flavones in hemp extracts, including cannflavins A and B, was also evaluated by HPLC.
The study on Cannabis volatile compounds was performed by developing a new method based on headspace solid-phase microextraction (HS-SPME) coupled with GC-MS and GC-FID. Cannabidiolic acid (CBDA) and cannabidiol(CBD) were found to be the most abundant cannabinoids in the hemp samples analysed, while β-myrcene and β-caryophyllene were the major terpenes. As regards flavonoids, cannflavin A was observed to be the main compound in almost all the samples.
The methods developed in this work are suitable for the comprehensive chemical analysis of both hemp plant material and related pharmaceutical or nutraceutical products in order to ensure their quality, efficacy, and safety.”
“Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands.
Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects.
We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics.
Most importantly, these bioactive compounds represent structurally new natural product chemotypes in the area of cannabinoid research and could be considered for further structural optimization as CB1 ligands.”
“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
“The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson’s disease.
Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson’s disease.
In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson’s disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson’s disease.”
https://www.ncbi.nlm.nih.gov/pubmed/30314601
https://www.sciencedirect.com/science/article/pii/S0074774218300692?via%3Dihub
“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
“Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states.
However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-line neuropathic pain medication gabapentin.
These findings indicate that gabapentin synergistically enhances the anti-allodynic actions of THC and improves its therapeutic window.
Thus, THC may represent a potential adjuvant for neuropathic pain medications such as gabapentin.”
https://www.ncbi.nlm.nih.gov/pubmed/30312630
https://www.sciencedirect.com/science/article/pii/S0028390818307779?via%3Dihub
“Cannabis is often used by consumers for sleep disorders.
Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC.
It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.”
“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.
The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.
CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.
CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”
https://www.ncbi.nlm.nih.gov/pubmed/30298064
https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full
“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