Tag Archives: cannabidiol

Medicinal cannabis: presenting possible treatment modalities for the future

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“Cannabis is the most popular recreational drug used in the world. It is estimated that 178 million people aged 15–64 years used cannabis at least once in 2012.

Cannabis or cannabinoids used to manage medical conditions is referred to as medicinal cannabis. There are various formulations of cannabis available on the market.

Cannabis can be administered orally, sublingually, or topically; it can be smoked, inhaled, mixed with food, or made into tea. It can be taken in herbal form, extracted naturally from the plant, gained by isomerization of cannabidiol (CBD), or manufactured synthetically.

The commercially available prescribed cannabinoids include dronabinol capsules, nabilone capsules, and the oromucosal spray nabiximols.

Canada and the Netherlands have government-run programs in which dedicated companies supply quality-controlled herbal cannabis. In the United States, 23 states and Washington, DC (May 2015) have introduced laws permitting the medical use of cannabis; other countries have similar laws.”

https://www.ncbi.nlm.nih.gov/pubmed/29870436

https://insights.ovid.com/crossref?an=01787381-201806000-00001

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.

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Molecular Neurobiology

“Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health.

Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans.

However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function.

These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway.

The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.”

https://www.ncbi.nlm.nih.gov/pubmed/29869197

https://link.springer.com/article/10.1007%2Fs12035-018-1143-4

Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

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“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.”

https://www.ncbi.nlm.nih.gov/pubmed/29867488

https://www.frontiersin.org/articles/10.3389/fphar.2018.00482/full

Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.

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BPS (Pharm)

“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.

The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC.”

https://www.ncbi.nlm.nih.gov/pubmed/26377899

“A number of studies now support the view that cannabidiol (CBD) may reduce the negative psychotropic effects of THC while enhancing its positive therapeutic actions. Our results are consistent with the notion that cannabis plant strains that contain THC and CBD at 1:1 ratios may be preferable to street cannabis for medicinal applications because they maximize therapeutic efficacy while minimizing the adverse effects of THC.”  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13333

Effects of cannabidiol plus naltrexone on motivation and ethanol consumption.

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“The aim of this study was to explore if the administration of naltrexone (NTX) together with cannabidiol (CBD) may improve the efficacy in reducing alcohol consumption and motivation rather than any of the drugs given separately.

The administration of CBD + NTX significantly reduced motivation and ethanol intake in the oral self-administration procedure in a greater proportion than the drugs given alone. Only the combination of both drugs significantly reduced Oprm1, TH and 5-HT1A gene expressions in the NAc, VTA and DR, respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD + NTX but had no effects by itself.

CONCLUSION AND IMPLICATIONS:

The combination of low doses of CBD plus NTX resulted more effective to reduce ethanol consumption and motivation to drink. These effects, appears to be mediated, at least in part, by 5-HT1A receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/29859012

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14380

“Naltrexone belongs to a class of drugs known as opiate antagonists. It works in the brain to prevent opiate effects (e.g., feelings of well-being, pain relief). It also decreases the desire to take opiates. This medication is also used to treat alcohol abuse. It can help people drink less alcohol or stop drinking altogether. It also decreases the desire to drink alcohol when used with a treatment program that includes counseling, support, and lifestyle changes.” https://www.webmd.com/drugs/2/drug-7399/naltrexone-oral/details

“Cannabidiol reduces ethanol consumption, motivation and relapse in mice. Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.”   https://www.ncbi.nlm.nih.gov/pubmed/28194850

Effect of tetrahydrocannabinol:cannabidiol oromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study.

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“To examine evolution in activities of daily living (ADL) in patients with multiple sclerosis spasticity during long-term use of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray.

Functional impairment was assessed retrospectively (prior to start of treatment) and at the present moment using a 16-item ADL survey; results were compared. A control group without add-on THC:CBD oromucosal spray was included to investigate possible recall bias.

RESULTS:

ADL was maintained or slightly improved with THC:CBD oromucosal spray across treatment time (mean 31.9 months) including significant improvement in ‘standing up’ (p < 0.05) and trends in other items. Significant improvements (p < 0.01) with THC:CBD oromucosal spray were observed in several multiple sclerosis spasticity-related symptoms. Overall, 96.9% of patients using THC:CBD oromucosal spray had a positive global impression of change during treatment.

CONCLUSION:

In this pilot study, THC:CBD oromucosal spray maintained or improved aspects of daily functioning. Further study in a larger trial is warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/29851356

https://www.futuremedicine.com/doi/10.2217/nmt-2017-0055

Investigational cannabinoids in seizure disorders, what have we learned thus far?

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“The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin and Δ9-tetrahydrocannabinolic acid.

Areas covered. In this review, the authors look at the results of pre-clinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR and SCINDEX databases.

Expert opinion. Pre-clinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.”

https://www.ncbi.nlm.nih.gov/pubmed/29842819

https://www.tandfonline.com/doi/abs/10.1080/13543784.2018.1482275

Cannabidiol effects on prepulse inhibition in nonhuman primates.

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“Prepulse inhibition (PPI) of acoustic startle reflex is a well-established behavior paradigm to measure sensorimotor gating deficits. PPI is disrupted in several neuropsychiatric disorders, including schizophrenia. PPI tests can be used to screen new drugs for treatment of such disorders.

In this review, we discuss how PPI paradigm can help in screening the therapeutic effects of cannabidiol (CBD).

We look into recent literature about CBD effects on PPI response in animal models, especially in nonhuman primates. CBD has been shown to modify PPI in N-methyl d-aspartate receptor antagonist models for schizophrenia, both in rodents and in nonhuman primates.

These results show CBD as a potential drug for the treatment of neurologic disorders that present alterations in sensorimotor system, such as schizophrenia. Moreover, the PPI paradigm seems to be a useful and relative simple paradigm to test the efficacy of CBD as a potential therapeutic drug.”

 https://www.ncbi.nlm.nih.gov/pubmed/29794254

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

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“The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments.

This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches.

This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids).”

https://www.ncbi.nlm.nih.gov/pubmed/29776349

“There is a need for more effective treatment approaches for cannabis dependent patients who are unable to discontinue their illicit use through psychosocial interventions alone. Longer-term agonist replacement treatment approaches rather than acute withdrawal management are likely to be more effective, with the combination of THC:CBD nabiximols preparation being potentially advantageous over synthetic THC analogues. This is the first large-scale outpatient RCT of nabiximols for this population, and has required the development of clinical and research methods specific to agonist treatment with a plant-derived cannabinoid formulation, building upon clinical research models previously used in opioid agonist treatment approaches.”

https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-018-1682-2

Sativex® as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial.

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“Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray (Sativex®) as add-on therapy to optimized standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity.

RESULTS:

Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically-relevant responders after 12 weeks (≥ 30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs 32.1%; P < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (P < 0.0001), mean pain NRS (P = 0.0013), and mean modified Ashworth’s scale (P = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns.

CONCLUSIONS:

Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.”

https://www.ncbi.nlm.nih.gov/pubmed/29792372

https://www.tandfonline.com/doi/abs/10.1080/00207454.2018.1481066