“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.
“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
“Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction.
Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms.
We show that repeated CBD treatment produces anxiolytic effects in the elevated plus maze test, increases the discrimination index of the novel object recognition task and attenuates cocaine-induced conditioned place preference but does not affect behavioural sensitization.
CBD reduced cocaine voluntary consumption and progressive ratio breaking point in the self-administration paradigm, but not drug-induced reinstatement. In parallel, CBD increased expression of type 1 cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor ratio in the striatum.
In summary, we show that CBD can modulate some behavioural and molecular manifestations of cocaine reinforcement. Moreover, our findings show that CBD has pro-neurogenic effects also in cocaine consuming animals.
Overall, this novel evidence provides new perspectives to use CBD as a therapeutic tool.”
https://www.ncbi.nlm.nih.gov/pubmed/30273593
https://www.sciencedirect.com/science/article/pii/S0028390818307135?via%3Dihub
“Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown.
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Anti-allodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), while the anxiolytic effect was blocked only by WAY.
Overall, repeated treatment with low-dose CBD induces analgesia predominantly via TRPV1 activation, reduces anxiety via 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.”
https://www.ncbi.nlm.nih.gov/pubmed/30157131
https://insights.ovid.com/crossref?an=00006396-900000000-98870
“Cannabaceae plants Cannabis sativa L. and Humulus lupulus L. are rich in terpenes – both are typically comprised of terpenes as up to 3-5% of the dry-mass of the female inflorescence.
Terpenes of cannabis and hops are typically simple mono- and sesquiterpenes derived from two and three isoprene units, respectively. Some terpenes are relatively well known for their potential in biomedicine and have been used in traditional medicine for centuries, while others are yet to be studied in detail.
The current, comprehensive review presents terpenes found in cannabis and hops. Terpenes’ medicinal properties are supported by numerous in vitro, animal and clinical trials and show anti-inflammatory, antioxidant, analgesic, anticonvulsive, antidepressant, anxiolytic, anticancer, antitumor, neuroprotective, anti-mutagenic, anti-allergic, antibiotic and anti-diabetic attributes, among others.
Because of the very low toxicity, these terpenes are already widely used as food additives and in cosmetic products. Thus, they have been proven safe and well-tolerated.”
“Movement disorders such as Parkinson’s disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.”
“The pharmacological importance of cannabidiol (CBD) has been in study for several years.
CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects.
Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas.
It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2.
This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties.
Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic.
More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies.
Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.”
“Cannabidiol (CBD), a non-intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side-effects and research showing it may modify drug cue salience.
We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side-effects.
When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.
A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.”
https://www.ncbi.nlm.nih.gov/pubmed/29714034
https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14243
“Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle.
The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design.
The drug did not induce any significant effect.
Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture.
Cannabidiol may play a therapeutic role in sleep regulation.
We found no differences between CBD and placebo in respect to polysomnographic findings or cognitive and subjective measures in a sample of healthy subjects. Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of CBD does not appear to interfere with the sleep cycle of healthy volunteers. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as evaluate the chronic effects of CBD in larger samples of patients with sleep and neuropsychiatric disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/29674967
https://www.frontiersin.org/articles/10.3389/fphar.2018.00315/full
“Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids.
Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1, CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase – FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95).
After 14 days, CBD injections (30 mg/kg) induced anxiolytic responses in stressed animals in the elevated plus-maze and novelty suppressed feeding tests, that were blocked by pre-treatment with a CB1 (AM251, 0.3 mg/kg) or CB2 (AM630, 0.3 mg/kg), but not by a 5HT1A (WAY100635, 0.05 mg/kg) receptor antagonist. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus. AM251 and AM630 abolished the effects of CBD on spines density. However, AM630 was more effective in attenuating the pro-neurogenic effects of CBD. CBD decreased FAAH and increased p-GSK3β expression in stressed animals, which was also attenuated by AM630.
These results indicate that CBD prevents the behavioral effects caused by CUS probably due to a facilitation of endocannabinoid neurotransmission and consequent CB1/CB2receptors activation, which could recruit intracellular/synaptic proteins involved in neurogenesis and dendritic remodeling.”
https://www.ncbi.nlm.nih.gov/pubmed/29510186
https://www.sciencedirect.com/science/article/pii/S0028390818301023