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The endocannabinoid system and Cannabidiol for the treatment of alcohol and other drug use disorders.

This new study from the magazine Frontiers aims to examine the role of the endocannabinoid system in drug-related disorders and the proposed pharmacological action in support of the therapeutic potential of cannabinoids in drug addiction, in particular the CBD: Nicotine, alcohol, psychostimulants, opioids and cannabis.

Although early research is promising, further studies on the efficacy of CBD will be needed in pre-clinical and clinical trials.

Alcohol and other drug use disorder is characterized by the repeated use of a substance, resulting in clinically significant distress, making it a serious public health problem.

The endocannabinoid system plays an important role in the common neurobiological processes that underlie alcohol and other drug-related disorders, particularly the mediating, rewarding and motivating effects of substance-related substances and indices.

A certain number of synthetic cannabinoids have been suggested as a potential pharmacological treatment for substance dependence.

Animal and human studies suggest that these cannabinoids have the potential to reduce cravings and relapses in weaning consumers, altering the reconsolidation of memory rewarding the drug, and inhibiting the rewarding effect of the drug reward. Drugs. These functions are probably due to the targeting of the endocannabinoid and serotoninergic systems, although the exact mechanism has not yet been elucidated.

Global symptom

Alcohol and other drug use disorders are a global problem, with more than 30 million people who have it. So far, treatment has had only minimal success, with a high probability of relapse. There is also no pharmacotherapy established reliably for single use medical devicessuch as cannabis and stimulant-related disorders. Current pharmacotherapies: substitution of opiates by methadone, Naltrexone for disorders related to alcohol consumption or nicotine replacement, are not very effective to prevent relapse. Single-use medical devices have been conceptualized as an inadequate and recurrent cycle of intoxication, intoxication, withdrawal and withdrawal that leads to excessive substance use despite adverse consequences.

Recent models question the major brain circuits involved in the importance of reward, motivation and memory / learning associations in maintaining dependency.

https://docplayer.fr/48837457-Le-circuit-de-la-recompense-et-la-dopamine.html

Synthesis of the endocannabinoid system

Le SCE consists of cannabinoid receptors (CB1R, CB2R), endogenous ligands that bind to these cannabinoid receptors [anandamide and 2-arachidonoylglycerol (2-AG)] and enzymes for their biosynthesis and degradation. During the last 10 years, the main focus has been on the CB1R, because of their presumed role in a range of physiological functions, including the psychoactive effect of THC. CB1R is one of the most common G protein-coupled receptors in the central nervous system, preferably residing on presynaptic neurons in various regions, including the neocortex, striatum and hippocampus. Their wide distribution allows them to guide a host of functions ranging from cognition, memory, mood, appetite, and sensory responses. Endocannabinoids themselves function as neuromediators that are released by postsynaptic neurons and bind to presynaptic CB1Rs to moderate the release of neurotransmitters, such as gamma-aminobutyric acid (GABA), glutamate, and dopamine. While the specific CB1R function depends on the cell population and the region in which they reside, their role in retrograde signaling allows them to regulate the signaling activity of cognitive, emotional and sensory functions, which gives them a therapeutic capacity.

Here is an explanatory video:

CBD facilitates the detoxification of drug substances

Γ-Aminobutyric acid (GABA) controls the release of dopamine. THC prefers that GABA be released, so that dopamine thrives, giving a "high", euphoria and activation of the reward system and causes dependence. It also controls the activity of the amygdala (stress, fear, center of anxiety), so when there is little Gaba, the amygdala becomes too active. The prolonged THC in the brain therefore causes anxiety, high levels of stress, which makes you want more THC to numb that feeling.

Evidence demonstrates the need for cannabinoid signaling on CB1Rs to induce long-lasting synaptic plasticity, such as trough long-term glutamatergic release in the dorsal and ventral striatum. Such functional changes, especially in the striatal structures responsible for the rewarding and motivating effects of alcohol and other drug abuse, are not only necessary to give importance to the reward, but also to establish a habit compulsive consumption. The endocannabinoid system is therefore a necessary contributor to cellular adaptation in the transition from recreational use of alcohol and other drugs to a consumption disorder.


Striatal structures in red

Phytocannabinoids, such as THC and CBD, modulate the level of brain activity in the limbic regions during emotion processing tasks. Endocannabinoids can further induce long-term changes in synaptic strength in the hippocampus, which promotes associative memory formation.

Dronabinol, a stereoisomer of THC, and nabilone, a synthetic analogue of THC, originally intended for nausea and weight loss, have been shown to be weaning cannabis. However, the dronabinol and nabilone can not prevent cannabis use or relapse.

Alcohol

In animal studies, CBD has been shown to be effective in reducing self-administration of ethanol and at a sufficiently high concentration (120 mg / kg but not 60 mg / kg), attenuated the relapse of ethanol. . Other animal studies show that CBD (at 15 mg / kg) effectively reduces the recovery of ethanol administration and stress, up to 138 days after treatment. However, a study revealed that CBD alone is not effective in mitigating ethanol sensitization, which is considered the first step in drug-related plasticity. comparatively, pure THC et a ratio of 1: 1 THC: CBD have been shown to be more effective in reducing ethanol sensitization.

Tobacco

In a study placebo-controlled 24 smokers, those who received a CBD inhaler significantly reduced the number of cigarettes smoked compared to the placebo group, despite the lack of reported difference in craving among the groups.

opioids

Early studies of the efficacy of cannabinoids in relieving morphine withdrawal symptoms and abstinence symptoms were conducted 40 years ago, with rodent models suggesting that CBD alone is not effective in relieving signs of morphine withdrawal. abstinence in rats, but CBD combined with THC (5 report: 1) was significantly. THC itself has been shown to be more effective than CBD in inhibiting morphine abstinence syndrome in mice. However, studies more recent studies show that CBD treatment blocked the morphine's facilitating effect. It has also been found that CBD has some effectiveness in heroin studies in the rat.

stimulants

Evidence of the efficacy of CBD for the use of stimulants is mixed. Neither CBD alone nor a ratio of 1: 1 of THC: CBD reversed the cocaine sensitization effect although the rimonabant did it. Evidence of the use of CBD for stimulant addiction in animals is low, an observational study Longitudinal 122 participants found that cocaine users who report having used cannabis to control their cocaine use reduced their cocaine use over a period of 3 years. Nevertheless, street cannabis usually contains small amounts of CBD and the results can not be extrapolated to therapeutic efficacy.

Summary and future directions

The CBD looks promising in terms of mitigating the negative effects weaning and reduce the motivation to self-administer or re-establish the use of drugs in animals. However, evidence of its effectiveness is limited and mixed.

The ability of CBD to relieve stress, anxiety and depressive symptoms can be a mediator of its therapeutic effect. Indeed, it has been found that CBD has a therapeutic potential for relieving emotional and cognitive disorders which may be induced by chronic substance use, proving its potential utility in mitigating the deleterious course of the impairment, particularly among adolescents who begin to consume.

In summary, some preliminary research supports CBD as a drug therapy. However, more studies are needed on humans and emphasizes that CBD treatment does not replace psychological treatment of addiction and that the best results will be obtained by combining CBD with a behavioral or psychosocial therapy adapted to addiction.

Table : The effectiveness of CBD for the treatment of substance use disorders.

Tags : cannabinoidsDrugNeurosciencepsychiatrysyntheticEndocannabinoid system