Transdermal Delivery of Cannabidiol Attenuates Binge Alcohol-Induced Neurodegeneration in a Rodent Model of an Alcohol Use Disorder

“Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration… the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration…

CBD is a main constituent of cannabis sativa… CBD is very well tolerated in humans. CBD has a plethora of actions, including anticonvulsive, anxiolytic, anti-relapse and neuroprotective properties, which make it an ideal candidate for treating multiple pathologies associated with alcohol use disorders…

These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.”

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Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

“Cannabis contains over 60 different terpeno-phenol compounds…

cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV) are known as non-psychoactive components of cannabis.

These compounds have shown anti-inflammatory, immunosuppressive, analgesic, anxiolytic and anti-cancer effects…

Cannabinoids may play a role in neuroprotection in disorders such as stroke, Parkinson’s disease, traumatic brain injury and epilepsy…

It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury…

Accumulating data now suggest that cannabinoid CB1 receptors contribute to neuroprotection… Emerging data now support the evidence of the anti-inflammatory action of CBD…

 We have previously reported that CBD  has a potent and long-lasting neuroprotective effect when administered both pre- and post-ischemia, whereas only pre-ischemic treatment with delta9-THC reduced the infarction size…

These results suggest that CBD may prevent post-ischemic injury progressively induced by ischemic stroke….

…anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.

The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.

In the last 10 years, it has been possible to demonstrate that CBD has the following unique therapeutic profile: 1) a cannabinoid receptor-independent mechanism, 2) long-lasting cerebro- protective effect after ischemic stroke, and lack of development of tolerance.

Moreover, CBD has almost no side effects, including psychotropic activity.

Preliminary studies highlight the fact that the multifunctional actions of CBD may lead to benefits in more complex systems within the brain after ischemic stroke.

CBD offers new therapeutic possibilities for treating ischemic stroke…”

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Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy

“Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis.

We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis.

Cannabidiol attenuates alcohol-mediated oxidative stress.

Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway…

Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol.

Cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms.

In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.”

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Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity

“Alcohol is the world’s most widely used psychoactive drug, but chronic, excessive alcohol consumption leads to permanent organ damage or death..

In the current study, we use a rat model of binge alcohol consumption to determine the potential of cannabidiol (CBD) as a neuroprotectant against ethanol-induced neurotoxicity…

…we evaluated CBD as a neuroprotectant in a rat binge ethanol model.

When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner.

This study provides the first demonstration of CBD as an in vivo neuroprotectant…

CBD protects against binge alcohol-induced damage.”

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Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

“We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI).

In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation…

The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant.

Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI.

Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.”

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Cannabidiol: promise and pitfalls.

“Over the past few years, increasing public and political pressure has supported legalization of medical marijuana.

One of the main thrusts in this effort has related to the treatment of refractory epilepsy-especially in children with Dravet syndrome-using cannabidiol (CBD).

Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products.

Cannabidiol is the major nonpsychoactive component of Cannabis sativa.

Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever.

These preparations were widely employed as analgesics by Western medical practitioners in the 19(th) century.

More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis.”

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Cannabis, cannabidiol, and epilepsy – From receptors to clinical response.

“The use of cannabis for medicinal purposes is becoming more prevalent.

For this purpose, various preparations of cannabis of varying strengths and content are being used.

The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations.

There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear.

Some suspect an existence of synergy or “entourage effect” between CBD and THC.

There is strong evidence that THC acts via the cannabinoid receptor CB1.

The mechanism of action of CBD is less clear but is likely polypharmacological.

The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy.

There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases.

Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.”

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Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.

“The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, ie., delta9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated…

The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity.

This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use.”

“Antiestrogen treatment of breast cancer: an overview.”

“Newly Found Estrogen Pathway Suggests Novel Breast Cancer Targets”

“New Estrogen Mechanism Holds Novel Cancer Treatment Promise”

“CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen.”

“Scientists discover new role estrogen plays in cancer growth”

“Antiestrogen-induced remissions in stage IV breast cancer.”

“Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.”

“New estrogen-related breast cancer mechanism detected”

“Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action… Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).”

“Anti-Estrogen Drugs to Treat Breast Cancer”


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Advances in the Management of MS Spasticity: Recent Observational Studies.

“Clinical trials demonstrate the efficacy and tolerability of an intervention under experimental conditions, but information on use under daily practice conditions is required to confirm the effectiveness and safety of new management options.

Clinical outcomes for THC:CBD oromucosal spray (Sativex®) in patients with treatment-resistant MS spasticity have been collected in post-marketing safety registries from the UK and Germany, a safety study from Spain and two observational studies from Germany, including one investigating its effects on driving ability.

Collectively, findings from daily practice support the long-term effectiveness and safety of THC:CBD oromucosal spray.

There was no evidence of abuse/misuse or other adverse events of special interest with a cannabis-based medicine and no impairment of driving ability.

Observational data and real world experience reinforce the efficacy and safety of THC:CBD oromucosal spray as reported in phase III clinical trials.”

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Advances in the management of multiple sclerosis spasticity: recent clinical trials.

“Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.


In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study.

THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use.

In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo.

Moreover, after 50 weeks’ treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change.

In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray.

In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms.

THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term.

A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use.”

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