Addiction is a major cause of death or decreased life expectancy in humans around the globe today. The most dangerous substances are tobacco, alcohol, and opioids which are all addictive, cause chronic health problems, and are a major burden for society. Estimates vary widely regarding the global deaths per year due to addiction and substance abuse, but are likely around 352,000 people per year, without including the largest contributor, tobacco smoking. In 2015, the WHO estimated that as many as 6 million people per year die prematurely due to the effects of tobacco smoke. Cannabis is the most widely used illicit substance in the world today, and is now also looking like a therapeutic that could help treat the addiction of more malevolent substances. Previously, we covered the ways in which cannabis legalization is decreasing binge drinking and opioid use in the USA, but today we will look at how researchers are using CBD in clinical trials to treat addiction for some of society's most problematic substances.
CBD is the second most abundant cannabinoid in the Cannabis sativa plant, and is non-psychoactive. Some studies have identified it as being important in modulating the effects of THC in the brain. CBD is also responsible for much of the observed health benefits of the cannabis plant, and has been instrumental in turning public opinion from seeing it as a drug, to seeing it as a medicine. But one of the more interesting uses that is now being trialed by researchers and neuroscientists like Dr. Yasmin Hurd of the Mount Sinai Hospital in New York, is addiction.
Why is CBD Being Explored for Drug Addiction?
Many who grew up during cannabis prohibition, listening to all the propaganda surrounding the plant, they may be thinking, "how are you going to treat drug addicts by giving them another drug?' But actually, the science of CBD and addiction is further along than many of the other health and wellness claims for the molecule. CBD may actually help to modulate or interrupt the typical reward circuits in the brain that are associated with addiction. There are multiple reward circuits, but the one most often attributed to drug or substance addiction is the dopamine circuit. This is basically the circuit in our brain which gives a bit of reward in the form of a burst of pleasant feeling dopamine when an expectation or need is met.
It was in 2015 that the first systematic review of CBD’s potential in treating addiction was published, which looked at about 14 studies on humans and rats and concluded that there was enough evidence in the areas of opioid, cocaine, and psychostimulant addiction, as well as some preliminary data on tobacco addiction, that warranted further investigation. That review noted that the effects of CBD on addiction are not only due to direct modulation of dopamine reward pathways, but also due to secondary effects such as stress reduction and neuroprotection. That review concluded that investigation of CBD was essential both due to its promise in a limited number of primary studies, but also because of the magnitude of the issue and the current lack of effective treatments. Since that time, the science has been moving forward, as evidenced by trials involving several different commonly abused substances, and a possible fast-track to FDA approval in the works.
CBD and Opioid Addiction
Opioids (heroin, morphine, OxyContin, fentanyl, etc.) are one of the leading causes of death due to substance abuse, after tobacco and alcohol. It is estimated that opioids led to the deaths of 110,000 people globally in 2017. As with most substances, the US leads the way in abuse and addiction, with 47,600 opioid deaths just in 2017 and more than 351,630 deaths from opioids from 1999-2016. Previously on this site we discussed how states with legal cannabis had 6-12% lower rates of opioid abuse than prohibition states. We assumed that was in a large part due to access of alternative, safer therapeutics and analgesics, but there may be more to the story.
In May of 2019 a randomized, placebo-controlled trial was published in which CBD was given to heroin addicts to test its effect on cue-induced drug craving and anxiety during heroin abstinence as well as positive or negative effects on cognition and physiology. That study concluded that one high dose of CBD daily (400 - 800mg) significantly reduced both the craving and anxiety normally associated with the presentation of relevant drug cues. These effects lasted at least 7 days after the initial 3-day experiment, as evaluated subjectively and shown using physiological markers for heart rate and salivary cortisol levels. The study also found no adverse side effects of the treatment. The mechanism for this observation can, in part, be explained by the findings of a 2012 study on morphine addicted mice, which found that CBD acts of the 5-HT(1A) receptors and inhibits the reward circuit associated with opioid consumption. A study which was replicated and confirmed in 2018.
In her letter to Science and Society in March of 2017, Dr. Yasmin Hurd discusses the fact that today we only have a handful of medications to treat opioid use disorders (methadone, buprenorphine, and naltrexone), all of which are still addictive and carry their own chronic and acute risks. She points out that, unlike these other medications, CBD will not be diverted to the black market, is non-rewarding, has a low lethality, and does not negatively interact with other opioid drugs (such as fentanyl). The letter goes on to describe the ways in which opioids and exogenous cannabinoids cause similar cascade reactions in the body, how CBD can help to mediate the dependance on opioid drugs, and called for many new clinical trials over the next few years. Furthermore, according to the US government database of clinical trails, there will be another trial to use CBD for the treatment of opioid addiction beginning in 2023, using the new polymer encapsulated nanosphere CBD drug APH-1501 developed by Aphios Pharmaceutical LLC.
CBD and Cocaine Addiction
Two of the most highly addictive drugs today are cocaine and nicotine, as both can be used habitually without much effect to normal life (unlike heroin or alcohol), causing deeply entrenched addictions that are difficult to break. Again, CBD has been shown to be helpful in reducing this reward seeking behavior, although through different mechanisms than with the opioids discussed above. From mouse studies, it would appear that CBD administration modulates neuronal proliferation in the hippocampus of the brain. While it does not decrease the need to the drug, it did reduce the attention given to relevant drug cues, implying that it could assist in treatment. This study was reinforced by a 2019 study that found that mice given CBD had lower rates of cocaine self-administration. However, so far there have been no published in vivo human studies for the use of CBD in controlling cocaine addiction.
CBD and Nicotine Addiction
As mentioned above, nicotine, or more accurately tobacco smoking, accounts for around 6 million early deaths globally each year. Nicotine is one of the most addictive substances, and also one of the most widely abused. One of the first major studies showing the promise of CBD in smoking cessation was in 2013. Although the study was not placebo controlled, it did show that by using a CBD inhaler, smokers looking to quit reduced consumption by 40%. A Placebo controlled follow up published in 2018 found that CBD administration reduced responsiveness to smoking cues, but did not reduce the overall desire to smoke or the withdrawal symptoms. It was concluded that CBD can be an effective aid to reducing response to smoking cues, however at this time no clinical trials are listed in the US government database.
CBD, Alcohol and Other Substances
Between the year 2000 and 2016, there were 425,045 deaths in just the USA that were directly attributed to alcohol abuse. So far, there is limited information on the use of CBD in the treatment of alcohol dependency. According to a study on mice, CBD reduced the self-administration of ethanol in mice, and reduced withdrawal symptoms such as hypothermia and convulsions. Furthermore, the study found that CBD reduced the relative expression of genes in the brain related to alcohol addiction. While promising, there have thus far been no published human trials
Methamphetamines are another addictive drug that is having widespread negative impacts on societies around the globe, particularly in South East Asia. Thus far, there has been one major study on CBD and methamphetamine consumption, a 2018 study in mice. That study did find that high dose CBD administration did reduce the self-administration of methamphetamines as well as reduced methamphetamine seeking behavior.
Cannabidiol, or CBD, was restricted from the medical community for more than 50 years, and during that time the world saw an increase in the prevalence and the destructiveness of addictive substances. Today, millions of people suffer with substance use disorders and addictions, many of which have few valid treatment options. Because of this, many of these cases unfortunetly end in death due to over-doses, injuries, and chronic health issues. There is a strong need for novel medications to help treat addiction, either in conjunction with therapy or independent of it, and CBD may either be that drug, or will help us find the way to it, as cannabis has done in so many other areas of modern-day medicine.