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 use disorders and the pharmacological action proposed in support of the therapeutic potential of cannabinoids in drug addiction, in particular CBD: in particular on the Nicotine, alcohol, psychostimulants, opioids and cannabis.
While early research is promising, further studies on the effectiveness of CBD will be needed in pre-clinical and clinical trials.
Alcohol and other drug use disorder is characterized by repeated use of a substance, which results 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 use disorders, particularly in mediating the gratifying and motivating effects of substances and substance cues.
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 craving and relapse in withdrawal users, by altering the reconsolidation of memory that rewards the drug and by inhibiting the reward facilitating effect of the drug. Drugs. These functions are likely due to the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism has not yet been elucidated.
Alcohol and other drug use disorders are a global problem, with more than 30 million people who are affected. So far, the treatment has had minimal success, with a high likelihood of relapse. There is also no reliably established pharmacotherapy for patients with 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 relapses. Single-use medical devices have been conceptualized as an inappropriate and recurrent cycle of intoxication, intoxication, withdrawal and craving that results in excessive substance use despite adverse consequences.
Recent models challenge the main brain circuits involved in the importance of reward, motivation and memory / learning associations in maintaining addiction.
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. Over the past 10 years, the main focus has been on CB1R, due to their presumed role in a whole range of physiological functions, including the psychoactive effect of THC. CB1Rs are 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 neurotransmitters which 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 enables them to regulate the signaling activity of cognitive, emotional and sensory functions, which gives them therapeutic capacity.
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 flourishes, resulting in a high, euphoria and activation of the reward system and causes addiction. It also controls the activity of the amygdala (stress, fear, anxiety center), so when there is little Gaba, the amygdala becomes too active. The prolonged THC in the brain therefore causes anxiety, high stress levels, which makes you crave 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 drinking. The endocannabinoid system therefore represents a necessary contributor to cellular adaptation in the transition from recreational alcohol and other drug use to a substance use disorder.
Phytocannabinoids, like THC and CBD, modulate the level of brain activity in limbic regions during emotion processing tasks. Endocannabinoids can further induce long-term changes in synaptic strength in the hippocampus, which promotes the formation of associative memory.
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.
In animal studies, CBD was 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 relapse of ethanol . Other animal studies show that CBD (at 15 mg / kg) effectively reduces recovery from ethanol administration and stress, for up to 138 days after treatment. However, a study found that CBD on its own is not effective in attenuating sensitization to ethanol, which is considered the first step in drug-associated plasticity. Comparatively, pure THC et a ratio of 1: 1 of THC: CBD have been shown to be more effective in reducing sensitization to ethanol.
In a study A placebo-controlled study of 24 smokers, those who received a CBD inhaler significantly reduced the number of cigarettes smoked compared to the placebo group, despite no reported difference in craving between groups.
The first studies on the effectiveness of cannabinoids in relieving morphine withdrawal symptoms and abstinence symptoms were performed 40 years ago, with rodent models suggesting that CBD alone is poorly effective in relieving signs of 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 treatment with CBD blocked the facilitating effect of morphine. CBD has also been found to have some effectiveness in heroin studies in the rat.
The evidence for the effectiveness of CBD for stimulant use is mixed. Neither CBD alone nor a 1: 1 ratio of THC: CBD reversed the sensitizing effect of cocaine although the rimonabant did it. The evidence for the use of CBD for stimulant addiction in animals is weak, an observational study Longitudinal study of 122 participants found that cocaine users who report using cannabis to control their cocaine use reduced their cocaine use over a 3-year period. However, street cannabis generally contains low amounts of CBD and the results cannot be extrapolated to therapeutic efficacy.
Summary and future directions
CBD looks promising in mitigating the negative effects withdrawal and reduced motivation to self-administer or restore drug use in animals. However, the evidence for its effectiveness is limited and mixed.
CBD's ability to relieve stress, anxiety, and depressive symptoms may mediate its therapeutic effect. Indeed, it has been found that CBD has therapeutic potential to relieve emotional and cognitive disorders which can be induced by chronic substance use, demonstrating its potential usefulness in reducing the deleterious course of impairment, particularly in adolescents who are new to use.
In summary, there is some early research supporting CBD as a drug therapy. However, more studies are needed in humans and stresses that CBD treatment is not a substitute for 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.