Cannabis is the most popular illegal drug. Some experts argue that cannabis as a gateway drug leads to the use of other drugs. In contrast, more and more studies show that cannabinoids can assist as an “exit drug” for addiction disorders. According to clinical studies, CBD can assist with nicotine, opioid, and cannabis withdrawal. Current surveys and studies show that THC- and CBD-containing cannabis alleviates opiate withdrawal symptoms for most individuals. Increasing legal access to recreational and medical cannabis in the U.S. is already showing positive effects on the use of other drugs: for example, states with legal access to cannabis have fewer opiate-related deaths. A study from Colorado showed that heavy alcohol users drink less alcohol and engage in less binge drinking on days when cannabis is used.
At what point does a dependency exist?
Dependence, colloquially known as addiction, is a global health problem. Worldwide, more than 30 million people were affected in 2017 [1]. Medical professionals diagnose the dependence syndrome according to different classification systems (ICD-10, ICD-11, DSM-IV or DSM-5) [2].
Characteristics of the dependence syndrome are [2]:
- Strong urge to consume (craving, addiction pressure)
- Loss of control
- Tolerance development
- Physical withdrawal symptoms
- Neglect of other interests and obligations
- Continued substance use despite harmful consequences
According to ICD-10, a dependence syndrome exists if three criteria occur repeatedly within one year or during one month. In the case of physical dependence, tolerance develops, the body becomes accustomed to the effect of the substance. Affected persons need a dose increase to achieve intoxication, withdrawal symptoms occur when stopping.
Psychological dependence is manifested by loss of control and compulsive use. Those affected want to experience the pleasant substance effect again and again or avoid unpleasant effects. Thoughts revolve only around the drug, other interests are neglected.
The newer ICD-11 also includes substances without dependence potential such as antidepressants, laxatives, or non-opioid painkillers. The non-substance-related addictions gambling disorder and online gaming disorder are also included [2].
What drugs can be addictive?
Substance-related disorders can be triggered by a wide variety of drugs [3]:
- Alcohol
- Coffeine
- Cannabis
- Hallucinogens (phencyclidine or similar arylcyclohexylamines and other hallucinogenic substances)
- Inhalants (“sniffing agents”)
- Opioids
- Sedatives (tranquilizers), hypnotics (sleeping pills), or anxiolytics (anxiety-relieving substances)
- Stimulants (amphetamine derivatives, cocaine, and other stimulants)
- Tobacco
- Other partly unknown substances (“designer drugs”)
Despite various effects, all drugs, when used in excess, can activate the reward system in the brain, whose most important neurotransmitter is dopamine [2,3]. The reward system is essential for survival, motivating desired behavior (e.g., eating) and playing a role in memory. However, psychotropic substances trigger such strong feelings of happiness (“high”) that normal everyday activities are neglected [3].
Dependency disorders are chronic diseases. Despite drug and psychological treatment, many of those affected relapse. Study data show that one year after completion of treatment, more than 85 percent of users of alcohol, nicotine, or illegal drugs relapse [4]. Among the reasons is the lack of effectiveness of available treatments. For certain addictions, for example cannabis, cocaine or amphetamines, no specific treatments are available to date. The endocannabinoid system regulates emotions, cognition, and reward system. Cannabis-based medications are therefore an interesting approach to effective and safe therapies for substance use disorders (SUD) [1,2].
Cannabidiol (CBD) for addiction disorders
Cannabidiol (CBD) is a non-psychotropic cannabinoid of the cannabis plant. Clinical studies demonstrate anticonvulsant, antianxiety, and antipsychotic effects. Preclinical and clinical studies show addiction-relieving effects. A 2021 systematic literature review showed that CBD may be a promising therapy for substance use disorders (SUD). The researchers evaluated 24 preclinical and 16 clinical studies.
Clinical studies showed positive influences in nicotine, cannabis, and opioid use disorders (e.g., in terms of frequency and quantity of use). In contrast to animal studies, no effect was seen in humans for cocaine or alcohol use disorders. However, the data to date is small, so further clinical studies are needed [5].
CBD acts at various receptors, including TRPV1 channels, serotonin, cannabinoid, and dopamine receptors. Scientists hypothesize that CBD may modulate the dopamine response and thereby reduce addictive behaviors. Further studies are needed to explore safety, efficacy, and mechanisms of action [6,7].
Cannabis use disorder (CUD)
The most widely used illegal drug is cannabis. In Europe, about one in four adults has experience with it. In Germany, about 3.11 million people in the population (18 to 64 years) used cannabis last year, which corresponds to 6.1 percent of the total population [8]. Between 2020 and 2022, the proportion of cannabis users in Spain was about 10.5 percent, about 7.1 percent in England, and about 11 percent in France. The data represent the results for the latest available surveys in each country. Participants in each study were between the ages of 15 and 64 [9].
Cannabis is less risky than most other drugs, but the risk of dependence should not be underestimated. About 10 percent of the 193 million cannabis users worldwide have a problematic consumption behavior. Those affected often suffer from other mental illnesses and substance dependencies. Psychotherapeutic approaches (e.g. behavioral therapy, motivational therapy, contingency management) can help reduce cannabis use. Medications for the treatment of cannabis dependence, including cannabidiol (CBD), are currently being researched [10].
Double-blind study: CBD for cannabis addiction
London researchers investigated non-psychotropic CBD for the treatment of cannabis use disorder (CUD) in a double-blind study published in 2021. 82 participants aged between 16 and 60 years took part in the phase 2a study, which consisted of two study sections. Affected individuals struggled with moderate or severe CUD according to DSM-5, reported at least one unsuccessful attempt to quit, and used tobacco. The research team examined how different doses of synthetic CBD affected cannabis use. Regular urine tests were used to monitor the concentration of the THC breakdown product THC-COOH, and participants also reported the number of abstinent days each week.
- First study phase (between May and August 2015): For 4 weeks, 48 participants took placebo capsules or CBD capsules of varying dosages (200, 400, or 800 mg total) twice daily. The researchers determined the ineffectiveness of the lowest CBD dosage and continued the study with the higher dosages.
- Second study phase (between May 2016 and January 2017): Anadditional 34 affected individuals took placebo or medium- or high-dose CBD for 4 weeks. Under CBD therapy, cannabis use decreased significantly: participants had fewer THC breakdown products in urine (decrease of 94 ng/ml and 72 ng/ml, respectively) and reported an increase in abstinence days (by 0.48 days/week and 0.27 days/week, respectively). CBD therapy was well tolerated overall with mild to moderate side effects.
The study results indicate dose-dependent effects of CBD, called biphasic effect by experts. While the lowest dose was ineffective, the higher doses were able to reduce cannabis use. The middle CBD dosage showed the greatest treatment success. Affected individuals were able to maintain reduced cannabis use at follow-up (June 2017), while this sustained success was absent at high CBD doses. Different outcomes were seen for cannabis withdrawal symptoms, tobacco use, sleep quality, and anxiety. Medium CBD dosage reduced cigarette use but worsened sleep. Cannabis withdrawal symptoms and anxiety were best alleviated by high-dose CBD. However, the researchers emphasize that long-term studies are needed. Further research will clarify whether CBD can independently reduce cannabis use or merely make cannabis withdrawal more tolerable [11].
Opioid use disorder (OUD)
Abuse and overdose of illegal opioids such as heroin, as well as opiate-based painkillers, are problematic. The greatest risk of opioid poisoning is potentially fatal respiratory paralysis. In the late 1990s, opioid-related deaths in the United States skyrocketed. The opioid fentanyl accounted for two-thirds of all opiate-related deaths in 2018, with 46,802 documented deaths [12]. Opiate withdrawal can cause a wide variety of symptoms, including anxiety, pain, sleep disturbances, and gastrointestinal symptoms. While acute withdrawal symptoms last one to two weeks, some symptoms may last for months [13].
Preclinical research showed that the endocannabinoid system plays a role in opiate withdrawal. THC and CBD, as well as increases in the endocannabinoid anandamide, have an alleviating effect on opiate withdrawal. Clinical studies in humans are scarce so far: two double-blind studies from 2015 and 2016 showed that the pure substance dronabinol (another term for THC) alleviates opiate withdrawal symptoms [14].
A 2022 literature search found that CBD can be used as an adjunct therapy in opiate withdrawal. CBD has antianxiety, antidepressant, anti-inflammatory, emetic, analgesic, and opioid craving-reducing effects. However, prospective double-blind studies are needed, as only preclinical studies and small clinical trials exist to date [13].
U.S.: Legal cannabis dispensaries linked to fewer opiate-related deaths
More and more U.S. states are legalizing cannabis. A study published in 2021 examined how legal cannabis provision affects opioid abuse. The research team examined county-level associations between the number of cannabis dispensaries and opioid-related deaths between 2014 and 2018. Data from all 812 counties in the 23 U.S. states that allowed medical and/or recreational cannabis by the end of 2017 were analyzed.
Data analysis found that increasing legal cannabis access is associated with reduced opioid-related deaths. Opening one more cannabis dispensary at the county level (increasing from one to two dispensaries) is associated with 17 percent reduced opioid-related deaths. For synthetic opioids such as fentanyl, deaths decreased by over one-fifth (21 percent). The results suggest associations between increasing prevalence of cannabis use and reduced opioid-related mortality [15].
Cannabis alleviates opioid withdrawal symptoms for most people affected
In some U.S. states, medical cannabis is used to treat opiate addiction. In 2020, a team of researchers at Johns Hopkins University used a survey of people with opioid addiction to investigate whether cannabinoids help or worsen opiate withdrawal. To do so, they surveyed 200 participants who had used cannabis and opioids in the previous month and had experience with opiate withdrawal. To this end, participants indicated which withdrawal symptoms were alleviated or exacerbated by cannabis. In addition, the severity of opiate withdrawal symptoms was assessed on days with and without cannabis.
More than half (62.5 percent) of the 200 participants used cannabis to relieve opiate withdrawal. According to the results, cannabinoids can alleviate numerous opiate withdrawal symptoms, including anxiety, tremors (shaking), and sleep disorders. However, for a small proportion of respondents (6.0 percent), cannabis increased symptoms, particularly yawning, watery eyes, and runny nose. Women reported greater symptom relief than men. Overall, the results show that cannabis can significantly alleviate opiate withdrawal. Only in isolated cases did medicinal cannabis worsen certain symptoms. Further clinical studies are needed [14].
Alcohol use disorder (AUD)
Despite its high-risk potential, alcohol is widely accepted in our society. In Germany, residents over the age of 15 consume an average of 11 liters of pure alcohol per year. Almost one in five (18.1 percent) drink risky amounts of alcohol. WHO data show that alcohol is responsible for six percent of all deaths.
WHO makes the following recommendations for low-risk alcohol consumption:
- Men should consume a maximum of 24 g (two standard drinks) and women 12 g (one standard drink) of pure alcohol per day.
- No alcohol should be consumed on at least two days per week.
With prolonged and high-dose alcohol consumption, physical dependence develops, and withdrawal results in various symptoms that can be life-threatening: Main symptoms are trembling, restlessness, sweating, sleep disorders and circulatory problems. Psychological disorders such as anxiety and depression are common. In severe cases, seizures or delirium may occur.
Excessive alcohol consumption results in numerous physical diseases: increased risk of injury, delirium tremens, seizures, liver cirrhosis, polyneuropathies, alcohol-related pancreatitis (inflammation of the pancreas). Alcohol consumption can be a contributor to numerous mental illnesses such as depression, schizophrenia, bipolar disorder, anxiety disorders, and personality disorders [16].
Little research has been done on whether cannabis can support alcohol addiction. A review published in 2019 showed that CBD can support alcohol withdrawal in preclinical studies. In animal studies, CBD counteracted alcohol-related nerve and liver damage and alleviated withdrawal-related cramps, among other effects. However, it remains to be clarified whether these effects are also seen in humans. Clinical studies are needed for this purpose [17].
Observational study: Colorado – less alcohol consumption due to cannabis use
An American observational study published in 2021 examined how cannabis use affects alcohol consumption and the likelihood of binge drinking among heavy alcohol users. Recreational cannabis has been legal in Colorado since 2014. The researchers also analyzed the influence of participant gender and cannabis use pattern (occasional or regular use). Between 2016 and 2020, 96 participants were recruited from university and community-based settings. Participants completed a Timeline Followback Form (TLFB) at baseline, four weeks, eight weeks, and five months to examine drinking behavior and cannabis use.
- On average, participants consumed one-third (29 percent) less alcohol if cannabis was used that day. Also, “binge drinking” was 2.06 times less likely on these days.
- No significant difference was found between regular and irregular cannabis users in terms of reduced alcohol consumption.
- There were no significant differences between men and women in terms of reduction of alcoholic beverages and “binge drinking” on days with cannabis use.
These results are consistent with previous observations that found that users consume less alcohol when they have legal access to cannabis [18]. In the first few years (between 2014 and 2016) after legalization of recreational cannabis in Washington, cannabis use increased while alcohol-related harms decreased [19].
Conclusion
Cannabinoids show great potential for treating addictions. Clinical studies have shown that cannabidiol (CBD) in particular can help people quit smoking [20] and support withdrawal from cannabis and opiates. However, research is still in its early stages. For example, preclinical studies show that CBD can alleviate even severe alcohol withdrawal symptoms such as convulsions, but studies in humans have yet to be conducted. If we take a look at the United States, we can already see that the availability of legal cannabis is reducing the use of other drugs such as alcohol and opiates. Therefore, larger clinical trials are welcome as well as basic research to understand how the body’s endocannabinoid system interacts with the reward system.
Sources
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