“Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations.
Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation…
These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.”
“Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumption, research efforts highlighting the biomedical consequences of the use of alcohol and cannabinoids are not only relevant to the substance abuse scientific field, but are also of public health interest.
Moreover, an overview of the recent literature about alcohol and cannabinoids neuro-immunomodulatory effects highlighting their future therapeutic potentials will provide a significant contribution to science and medicine.
Therefore, in the current review, we will first discuss briefly the prevalence of alcohol and marijuana abuse, followed by a discussion on the individual effects of alcohol and cannabinoids on the immune system; then, we will focus on the role of endocannabinoids on the alcohol-induced inflammatory effects.
In addition, the review also incorporates cytokine array data obtained from human monocyte-derived dendritic cells, providing a different perspective on the alcohol and cannabinoid abuse divergent effects on cytokine production.
The final section will highlight the therapeutic potential of cannabinoid receptors and the novel strategies to treat alcohol dependence as determined by in vitro, in vivo and clinical studies.”
“Under some conditions, stress, rather than directly triggering cocaine seeking, potentiates reinstatement to other stimuli, including a subthreshold cocaine dose.
Endocannabinoid signaling is increased by stress and regulates synaptic transmission in brain regions implicated in motivated behavior.
The objective of this study was to test the hypothesis that cannabinoid type 1 receptor (CB1R) signaling is required for stress-potentiated reinstatement of cocaine seeking in rats…
These findings demonstrate that footshock stress increases prefrontal cortical endocannabinoids and stress-potentiated reinstatement is CB1R-dependent, suggesting that CB1R is a potential therapeutic target for relapse prevention, particularly in individuals whose cocaine use is stress-related.”
“The role of the cannabinoid (CB) system in the tolerance to analgesic effect of opioid remains obscure. The aim of the present study was to evaluate the effects of the endocannabinoid nonselective receptor agonist anandamide (AEA) and CB1 receptor antagonist rimonabant (SR141716) on morphine analgesia and tolerance in rats.
The findings suggested that AEA in combination with morphine produced a significant increase in expression of analgesic tolerance to morphine.
Conversely, cannabinoid receptor antagonist SR141716 attenuated morphine analgesic tolerance.
In addition, administration of AEA with morphine increased morphine analgesia.
In conclusion, we observed that the cannabinoid receptor agonist anandamide and CB1 receptor antagonist SR141716 plays a significant role in the opioid analgesia and tolerance.”
“This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients.
The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction.
Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.”
http://www.ncbi.nlm.nih.gov/pubmed/19958538
“The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.
This brings up two important points. First, self determination, the right of an individual to decide which treatment or substance is most effective and least harmful for them. If an individual finds less harm in cannabis than in the drug prescribed by their doctor, do they have a right to choose? Secondly, the recognition that substitution might be a viable alternative to abstinence for those who are not able, or do not wish to stop using psychoactive substances completely.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795734/
“The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes.
Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances.
Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients.
The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances,”
“The vast therapeutic potential of cannabinoids of both synthetic and plant-derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies.
In addition, some observations indicate that cannabinoid receptor antagonists may be useful for the treatment of alcohol dependence and addiction, which is a major health concern worldwide.
While the synergism between alcohol and cannabinoid agonists (in various forms) creates undesirable side effects when the two are consumed together, the administration of CB1 antagonists leads to a significant reduction in alcohol consumption.
Furthermore, cannabinoid antagonists also mitigate alcohol withdrawal symptoms.
Herein, we present an overview of studies focusing on the effects of cannabinoid ligands (agonists and antagonists) during acute or chronic consumption of ethanol.”
“Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.
The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor.
Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC.
This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
These data indicate that THC increases pregnenolone through activation of the CB1 receptor…
In conclusion, this new understanding of the role of pregnenolone has the potential to generate new therapies for cannabis dependence.”
“Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication.
The major active ingredient of Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor.
This steroid has been shown to inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC.
While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction.
In this hypothesis, we caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation.
Blocking CB1 receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling.
Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels…”
“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders.
Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties.
Its effects against cocaine neurotoxicity, however, has remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms.
In conclusion, CBD protects against seizures in a model of cocaine intoxication.
CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.”