Most Impactful Studies on Cannabis

What cannabis research proves about health (and doesn’t).

Cannabis scientist studying plant

With the increasing move towards legalization of cannabis, ongoing medical marijuana programs in most states and the explosion in popularity of CBD, the landscape for cannabis research is improving for basically the first time in the plant’s long history.

Of course, many people have experiences and personal views on whether THC, CBD or a combination of cannabinoids are useful for specific issues, and views more broadly on cannabis and its benefits and downsides, but what really matters is evidence.

While there are still many limitations to what we know – you can’t shake off over half a century of prohibition like a cold – there are still plenty of studies on both CBD and THC that provide some tantalizing hints or outright proof that we’re moving in the right direction. Here are some of the most impactful studies on cannabis and CBD.


CBD for Drug-Resistant Seizures in Dravet Syndrome

“Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome” (2017)

Original study ›

Background

Undoubtedly the most evidentially-supported benefit of CBD is for the treatment of seizures in the rare seizure condition Dravet syndrome. The story of Charlotte Figi led to skyrocketing awareness of the potential benefits of CBD for the condition, and researchers quickly initiated a series of studies on the topic. The most important was a double-blind, placebo-controlled trial published in the New England Journal of Medicine.

What They Did

Researchers randomly assigned 120 children and young adults with Dravet Syndrome – basically a rare form of epilepsy – to either receive CBD or a placebo in addition to standard seizure treatment. They took four weeks’ worth of data for a baseline data, and then compared this with a 14-week treatment period, looking for a reduction in seizure frequency.

The Results

The results showed that those treated with CBD in addition to standard antiepileptic medication saw a reduction in seizures per month from 12.4 to 5.9 (on average), while those given a placebo in addition to standard treatment only saw a decrease from 14.9 to 14.1. In addition, 43% of the CBD group had their seizures reduced by half or more, compared with 27%t for those taking the placebo, and 5 percent had seizures stop entirely, compared to none in the placebo group. There were some side effects such as diarrhea (31% of CBD patients vs. 10% of the placebo group) and vomiting (15% CBD vs. 5% placebo), but the results showed that CBD is an effective treatment. These effects will also be dose-dependent, and in 89% of cases they were mild to moderate in severity.

What It Means

CBD can reduce seizures in people with Dravet syndrome, with some side effects.

Who Funded It?

The study was funded by GW Pharmaceuticals.

CBD Reduces Anxiety in Simulated Public Speaking Test

“Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients” (2011)

Original study ›

Background

The most common reason people use CBD is to manage anxiety, so evidence on this point has the potential to impact more users than for any other condition. The evidence for this is quite limited, but the most impactful study used a simulated public speaking test to investigate the potential benefit of CBD. It’s only preliminary research (and there have been slightly bigger studies with the same findings), but it was a powerful “proof of concept” in humans for the most common use of CBD.

What They Did

The study looked at 24 patients with social anxiety disorder, who were randomized to either receive 600 mg of CBD or a placebo, with another group of 12 non-anxiety sufferers going through the test without medication. The participants were evaluated at several points in the speaking test to gauge their anxiety level.

The Results

The group pre-treated with CBD showed reduced anxiety, cognitive impairment, discomfort and alert during the test, compared to the group treated with placebo. Actually, the response from the people with social anxiety treated with CBD wasn’t significantly different to the group without social anxiety. The bigger study mentioned in the previous paragraph obtained similar results with a real-life public speaking test, but the initial study still had a larger impact overall.

What It Means

CBD may reduce social anxiety, possibly to the point where people with social anxiety experience similar levels to people without the condition.

Who Funded It?

Grants from the São Paulo Research Foundation (FAPESP).

Cannabis Helps with Chemotherapy-Related Nausea

“Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy” (2015)

Original study ›

Background

One of the longest-running uses for cannabis in a medical setting is in the management of nausea related to chemotherapy and for other people taking a lot of medication for ongoing health conditions. This paper looks at chemotherapy patients specifically.

What They Did

This paper is unlike many of the others in this list because it’s actually a meta-analysis, combining the results of 23 randomized controlled trials to strengthen the conclusions they were able to draw. The studies all focused on the use of cannabis (with a focus on THC) to help with the nausea and vomiting from chemotherapy treatment. However, the trials were generally a little old (from 1975 to 1991) and only smaller numbers were able to be used for each comparison. The studies either compared cannabis-based medicine to a placebo or to the standard antiemetic treatment at the time.

The Results

Patients generally preferred cannabis to the placebo, and those receiving it were more likely than those on the placebo to report their nausea or vomiting completely stopping. There was more chance of side effects with cannabis, and – unsurprisingly – people were more likely to report “feeling high” when taking it. Overall, participants were 7 times more likely to drop out as a result of side effects from cannabis compared to the placebo, but 20 times less likely to drop out because the medicine wasn’t working. There was no difference between cannabis and the standard treatment at the time, but again side effects such as dizziness were more common in those taking the cannabinoid medicine, with people being 4 times more likely to drop out because of adverse events.

What It Means

The results are promising, and suggest that people receiving chemotherapy could see a reduction in nausea if they also took CBD. However, more studies need to be conducted for researchers to be able to make firm recommendations, and it’s unlikely to become a widespread treatment because of side effects.

Who Funded It?

The review was supported by the National Institute for Health Research (NIHR), while the individual studies discussed had various funding sources.

CBD Relieves Schizophrenia Symptoms

“Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia” (2012)

Original study ›

Background

With schizophrenia being one of the most commonly-cited risks of cannabis use, the news that CBD actually helps with the psychotic symptoms of the condition might be a bit of a surprise. However, as with many different effects, CBD and THC are very different substances. While THC may pose a risk for those already susceptible to psychological illness, the picture is pretty complicated.

Firstly, you have to disentangle the short-term effects of cannabis from an actual disorder (since it produces changes in perception after using it). But secondly – and more importantly – there are some inconsistencies, such as the rise in cannabis use over the past decades being accompanied by a decrease in schizophrenia. Generally speaking, it’s estimated that a third of cannabis users may be susceptible to psychosis and neurosis, but the other two thirds are not.

But in any case, the issue is with THC rather than CBD, and there is plenty of evidence on this point. In fact, this landmark study found that CBD use by people with schizophrenia leads to significant clinical improvements.

What They Did

The study used a randomized controlled trial design, recruiting 42 inpatients with acute paranoid schizophrenia, and randomizing them to receive either CBD or amisulpride (a strong antipsychotic medication).

The Results

The results showed that both treatments led to significant improvements, but CBD was considerably better in terms of side effects, which were mild compared to the existing treatment. The researchers attribute the success of CBD to its impact on the endocannabinoid anandamide (a cannabis-like molecule produced within the body), and point out that it could open a completely new avenue of treatment for people with schizophrenia.

What It Means

CBD could have big enough benefits for people with schizophrenia to be clinically relevant, but more research is needed.

Who Funded It?

Grants from the Stanley Medical Research Institute (FML) and the National Institute on Drug Abuse (DP).

Higher-THC Cannabis is More Strongly Associated with Psychosis

“The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study” (2019)

Original study ›

Background

Another aspect of the link between cannabis and schizophrenia is that if THC is the main concern (which it very much seems to be), you would expect that higher-THC cannabis was a bigger risk. While this isn’t something you can directly test in a randomized trial sort of way, there are ways you can tease out the details of the relationship.

What They Did

The researchers in this study used a case-control design, so they found people who had first-episode psychosis (901 in total) and matched them with controls (1,237) so they could be compared in terms of their cannabis use. The study took place at 11 sites across Europe and Brazil, and they split the cannabis use into low potency (less than 10% THC) and high potency (over 10% THC) to compare the effects.

The Results

They found that daily use of cannabis was associated with a 3.2-times increase in risk compared to non-use, but for high potency cannabis the risk was even higher, at 4.8 times a non-users’ risk. This led the researchers to calculate the reduction in cases of first-episode psychosis if high potency cannabis wasn’t available, with 12.2% of cases being avoidable according to their analysis, with bigger proportions in London and Amsterdam.

What It Means

The link between cannabis and psychosis is stronger when the THC content of the cannabis is higher. In other words, the link is likely to do with THC and higher-THC strains are associated with a bigger risk.

Who Funded It?

The study was funded by various governmental health services, particularly in the UK and Brazil.

Cannabinoids for Pain Management

“Cannabinoids in the management of difficult to treat pain” (2008)

Original study ›

Background

Another of the most evidentially-supported uses for cannabis medicines is for pain management, and Sativex (an equal mix of THC and CBD in spray form) has been approved as a pain treatment in Canada since 2005. There is a lot of research on the topic, but a review of the evidence from 2008 covers many of the early studies in detail, and has picked up hundreds of citations over the past decade. It’s also available in full for free, so it’s a great source of information and a place to find studies addressing specific questions.

What They Did

The author looked through the evidence on the use of cannabis in pain conditions and provides a narrative-style review of the results and theoretical background.

The Results

The review covers the randomized controlled trials that led to the approval of Sativex, with studies showing that it’s both safe and effective in the treatment of neuropathic pain, cancer pain and rheumatoid arthritis. Generally, the recommendation is to add the cannabis medicine to existing pain management regimes, but within this context it has some solid evidential support. For pain in particular, the benefit of only very minor side effects is substantial, because the opioids usually used for pain can have fairly serious side effects and pose a substantial risk of addiction.

What It Means

There is a lot of potential for cannabinoids to be combined with existing pain medications in the future, with a good deal of evidence to support their use.

Who Funded It?

The study was conducted by an employee of GW Pharmaceuticals.

CBD Reduces Cravings in People with Heroin Addictions

“Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial” (2019)

Original study ›

Background

While people less involved with cannabis or CBD as a topic may lump CBD together with recreational use of cannabis, this study shows that reality is much more complicated, and CBD may actually help people with heroin addictions.

What They Did

The study used a randomized controlled trial design, where 42 participants (who were abstinent from heroin but had heroin use disorder) were randomized to either receive CBD (400 or 800 mg per day for three consecutive days) or a placebo, with the aim of comparing each group’s responses to “drug cues” vs. neutral cues. Generally this would lead to drug cravings and anxiety.

The Results

The results showed that CBD significantly reduced both cravings and anxiety in response to the drug cues, compared to the placebo. Not only this, although the participants only received the doses of CBD for three days, the effects persisted and were still detectable seven days after the last dose. In addition, CBD reduced physical responses to the drug cues, such as levels of the stress hormone cortisol in the participants’ saliva and their heart rate.

What It Means?

CBD appears to be a very promising treatment for people with an addiction to heroin, particularly thanks to its low risk profile.

Who Funded It?

The study was funded by GW Pharmaceuticals and the Icahn School of Medicine at Mount Sinai.

States with Medical Marijuana Laws Prescribe Less Opiates

“Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population” (2018)

Original study ›

Background

The opioid crisis is an ongoing problem, starting from the 90s and continuing to the current day, with almost 50,000 people dying from opioid-related overdoses in the US in 2019, and approximately 80% of people who use heroin starting out by misusing prescription opioids. This is why finding alternatives that actually work is a huge priority for public health. Along with the evidence showing that cannabis-based medicines can be effective treatment for pain, there are several studies that find a link between the amount of opioid-based painkillers prescribed in a state and medical marijuana laws.

What They Did

One important example is this study, which looked at opioid prescribing in Medicare D patients and state-level medical marijuana laws between 2010 and 2015. During this time, there was an average of 23.08 million daily doses of opioids dispensed under part D of Medicare, and related deaths increased dramatically between 2000 and 2015.

The Results

However, in the analyses, researchers found that there were fewer daily doses dispensed in states with medical marijuana programs. They also found differences related to the type of program in place, with states that included dispensaries having 3.742 million fewer doses, compared to 1.792 million fewer doses in states where patients had to grow their own cannabis. There were also some differences dependent on the specific opioid, with hydrocodone and morphine showing statistically significant decreases in states with medical marijuana programs.

What It Means

Overall, the researchers conclude that medical cannabis reduces opioid prescriptions in general, particularly when there are dispensaries available.

Who Funded It

The University of Georgia.

Cannabis Doesn’t Affect Young Adults’ Brain Functioning in the Long-Term

“Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults” (2018)

Original study ›

Background

Another common claim about cannabis is the “this is your brain on drugs” type statement, implying that using weed (even occasionally) will reduce your ability to think or function beyond the acute effect of being high. This has been investigated a lot by scientists, and this meta-analysis addresses this question specifically.

What They Did

By combining the results of multiple studies, meta-analyses essentially generate one large study from several smaller ones. In total, they combined 69 studies, with a total of 2,152 cannabis users and an additional 6,575 with “minimal” use as a comparison group. The researchers compared results of neurocognitive tests administered in the original research papers to attempt to determine whether frequent or heavy use leads to cognitive dysfunction.

The Results

The results showed that frequent and heavy cannabis use was associated with a slight reduction in cognitive functioning, with no variation when they compared users who started at different ages. However, when the researchers looked specifically at studies that required 72 hours of abstinence prior to the test, there was no significant difference between users and non-users.

What It Means

Essentially, the evidence shows that while there are some small differences in cognitive functioning for heavy users (which the authors say “may be of questionable clinical importance”), being abstinent for a few days basically removes any differences.

Who Funded It?

The study was funded by a Department of Veterans Affairs Career Development Award.

CBD is a Promising Treatment for Acne

“Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes” (2014)

Original study ›

Background

Although it might seem like a relatively far-fetched use of CBD, the body’s endocannabinoid has a role to play in multiple systems in the body, including skin cell growth, and managing acne is one reason many people use CBD.

What They Did

Of course, there’s a difference between testimonials and individual experience and the actual science of the situation, so researchers investigated the impact of CBD on cultured human skin cells to see if the reported effects have a genuine biochemical basis.

The Results

The researchers found that applying CBD to the skin cells disrupted many of the processes involved in the development of acne. It also had anti-inflammatory effects, another key factor in the development of acne.

What It Means

The researchers conclude that due to the lipostatic, antiproliferative and anti-inflammatory effects of CBD, it holds promise as treatment for acne. This is one area where more research is definitely needed (for example, positive results in vitro may not apply to the real-world situation), but the signs so far are positive.

Who Funded It?

Several government grants, including one from the European Union.

No Association Between Cannabis Use and Lung Cancer

“Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study” (2006)

Original study ›

Background

Researchers expected cannabis smoking to cause lung cancer for understandable reasons: like the smoke from cigarettes, marijuana smoke contains carcinogenic compounds, and you would expect inhaling this on a regular basis to lead to lung cancer in users. However, when researchers have tried to conduct real-world studies to detect this link, the results have been inconsistent.

What They Did

This study aimed to investigate the issue by comparing a group of 1,212 people with cancer to a group of 1,040 controls (i.e. without cancer), matched with the cases in terms of age, gender and general socioeconomic status.

The Results

The results showed that there is an association between the number of “joint-years” of smoking (where one joint-year is the equivalent of smoking one joint a day for a year) and various cancer types, this was only the case when researchers didn’t correct for other factors. When they made adjustments for factors such as cigarette smoking, there were no associations with any cancer type for either 30 or 60-plus joint years of smoking. The researchers acknowledge that there may be some bias in the study design (e.g. bad estimates of lifetime smoking), but stress that the relationship can’t be particularly strong, or could even be so low it would be difficult to reliably detect it in research.

What It Means

It’s unlikely that cannabis smoking is a substantial cause of lung cancer – there might be an association, but if so, it is small.

Who Funded It?

Several US government grants.

Conclusion

Research into the medical effects of cannabis – or even research more generally – is still being hampered by regressive laws around the world, but the move towards legalization in many places and increasing acceptance of medical uses has improved the outlook substantially.

A lot of the results of the studies included in this post need to be confirmed by further research, but with so many lines of evidence pointing to various benefits of cannabis and an overstatement of the risks in the past, the future of cannabis research will likely reveal even more benefits to the plant and its cannabinoids.