“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.
“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
“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
“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
“Multiple sclerosis (MS) is an autoimmune disease leading to the destruction of myelin with consequent axonal degeneration and severe physical debilitation. The disease can be treated with immunosuppressive drugs that alleviate the symptoms and retard disease aggravation. One such drug in clinical use is glatiramer acetate (Copaxone).
The non-psychotropic immunosuppressive cannabinoid compound cannabidiol (CBD) has recently been shown to have beneficial effects on experimental autoimmune encephalomyelitis (EAE). The aim of our study was to compare the efficacy of CBD and standardized extracts from a CBD-rich, ∆9-THClow Cannabis indica subspecies (Avidekel) with that of Copaxone.
Our data show that CBD and purified Avidekel extracts are as efficient as Copaxone to alleviate the symptoms of proteolipid protein (PLP)-induced EAE in SJL/J mice. No synergistic effect was observed by combining CBD or Avidekel extracts with Copaxone.
Our data support the use of Avidekel extracts in the treatment of MS symptoms.”
https://www.ncbi.nlm.nih.gov/pubmed/30291491
https://link.springer.com/article/10.1007%2Fs10787-018-0536-3
“Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and others have been suggested. It seems that the endocannabinoid system is also involved in the pathogenesis and treatment of depression, though its role in this mental disease has not been fully understood yet. Both the pro- and antidepressant activity have been reported after cannabis consumption and a number of pre-clinical studies have demonstrated that both agonist and antagonist of the endocannabinoid receptors act similarly to antidepressants. Responses to the cannabinoid agents are relatively fast, and most probably, the noradrenergic, serotoninergic, glutamatergic neurotransmission, neuroprotective activity, as well as modulation of the hypothalamic-pituitary-adrenal axis are implicated in the observed effects. Based on the published data, the endocannabinoid system evidently gives novel ideas and options in the field of antidepressant treatment, however further studies are needed to determine which group of patients could benefit from this type of therapy.”
https://www.ncbi.nlm.nih.gov/pubmed/30290188
https://www.sciencedirect.com/science/article/pii/S0024320518306040?via%3Dihub
“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.
https://www.epilepsybehavior.com/article/S1525-5050(18)30483-9/fulltext
“Cannabinoids are widely used in the management of pain, nausea and cachexia in cancer patients. However, there has been no objective clinical evidence of any anticancer activity yet.
The aim of this study was to assess the effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer patients.
Clinical responses were seen in 92% of the 119 cases with solid tumours including a reduction in circulating tumour cells in many cases and in other cases, a reduction in tumour size, as shown by repeat scans. No side-effects of any kind were observed when using pharmaceutical grade synthetic cannabidiol.
Pharmaceutical-grade synthetic cannabidiol is a candidate for treating breast cancer and glioma patients.”