CATR: To start, could you tell us a little about your work around substance use disorders, and specifically your experience with cannabis and adolescents?

Dr. Gray: A large focus of my career has been on doing National Institutes of Health–sponsored research into better understanding substance use disorders in young people. So, that would include adolescents and young adults.

 

CATR: I’m sure during your research into cannabis, you’ve looked at how higher potencies today are leading to not only greater impairment, but also longer-term effects on brain development and cognition in adolescents. Can you tell us more about what you’re learning?

Dr. Gray: Sure, and I think this is part of the real education we have to do with parents, who may have smoked pot themselves 20 or 30 years ago and still think that it’s fairly harmless. The cannabis of today is different and much stronger than the cannabis of even 10 years ago. Growers and producers have gotten good at creating cannabis with much higher concentrations of tetrahydrocannabinol (THC), the cannabinoid that causes the high. In 1995, the average potency based on THC in marijuana was 4%. By 2014, the average potency had risen to approximately 12% (ElSohly MA et al, Biol Psychiatry 2016;79(7):613-619). Today, there are even some concentrated forms of cannabis that contain 80%–90% THC.

 

CATR: Right, and I know that there are also some great unknowns with synthetic cannabis, which might even make it riskier on the brain than the more natural form of marijuana. What’s your take here?

Dr. Gray: I would say yes, that’s very true. Other than anecdotal information, we know so little about synthetic cannabinoids, but we’re starting to get some more data. For example, we’ve known about the association between marijuana use and schizophrenia for decades, but now we’re starting to see a number of clinical reports of increases in psychotic effects with synthetics (Fantegrossi WE et al, Drug Metab Rev 2018:1–9). Synthetics vary in dose and constituency—partly because the DEA bans certain substances, and then the manufacturers try to get around that by using different cannabinoids. There are some big unknowns here. So, while I would tell patients that the safest thing is to not partake of any form of cannabis, they should know that synthetics are certainly riskier than naturally grown marijuana.

 

CATR: So, tell us more about what we should tell parents when their kids defend their excessive marijuana use—especially when the kids say things like, “Well, it’s safer than alcohol,” and, “Don’t doctors recommend cannabis for medical use?”

Dr. Gray: Yes, those are all things that I hear. With teen patients, rather than the confrontational approach, I tend to take the motivational interviewing approach, emphasizing rapport and dialogue building, avoiding aggressive confrontation and judgment, using open-ended questions, “rolling with resistance,” and gently working toward stepwise opportunities for behavior change. And I certainly encourage parents to be non-confrontational and have a gentle discussion around some of the fallacies that may exist in the argument that cannabis is beneficial. Kids sometimes argue that cannabis is natural and therefore benign. But what I’ll say to young patients is that there are many things in our natural world that are not benign and not so therapeutic. Many poisons occur naturally that we ought not to interact with. Here’s an example that I often use: Warfarin can be a lifesaving medical therapeutic for some people—it’s also the active ingredient in rat poison.

 

CATR: And what about a young person’s argument that smoking pot is less dangerous than drinking alcohol?

Dr. Gray: I think the first concern about saying it’s “safer than alcohol” is that you’re trying to establish a safety comparator between two substances that both have dangerous implications for a developing brain and are each associated with significant harms. That’s not really the best way to benchmark whether something is safe. I also think it’s unusual for adolescents to specifically choose one substance versus another. It’s been my experience, and studies have shown, that co-use of alcohol and marijuana tends to be more the rule than the exception (Patrick ME et al, Am J Drug Alcohol Abuse 2017;10.1080/00952990:1–11). On this one, you should be firm in explaining to young patients that both substances can be harmful.

 

CATR: But we all know that adolescents can be stubborn on this point, especially with the big trend toward medical marijuana and full legalization in several states. What else should we be telling teen patients who insist that cannabis is safe and therapeutic for them?

Dr. Gray: The thing they need to understand is that—while there might be a positive risk-benefit profile for someone with neuropathic pain, who is using cannabis in the context of an end-stage illness—the risk-benefit ratio is very different for a healthy adolescent user. This is where, though, I think it’s important for parents and for practitioners to avoid the polarizing potential of false equivalency. I try to step back from that, and let young patients know that I don’t consider cannabis to be a vile thing that should be removed from the Earth. I do think it contains ingredients that could be developed into medical therapeutics, and that there is considerably less risk to otherwise healthy adults who occasionally use cannabis. Then again, I also let young patients know that 1 in 11 adult and 1 in 6 adolescent cannabis users meet the criteria for cannabis use disorder (Hall W, Int J Drug Policy. 2009;20(6):458–466). For some people, cannabis is benign when used in moderation; the same is true for alcohol. But people who use frequently can and do develop the classic symptoms of cannabis use disorder.

 

CATR: And what about adolescents and adults who still say that they feel cannabis isn’t addictive?

Dr. Gray: You need to let them know that there’s a very well-characterized withdrawal syndrome with cannabis, and there’s also a tolerance that develops. People do get into the pattern where they use despite adverse psychosocial consequences. So, people do get addicted. What I let adolescents know is that they actually have a higher rate of getting addicted based on exposure than adults do. And that might not only be specific to cannabis—adolescents tend to have higher propensity toward problematic use of any substances. Let’s face it: Addictive substances, especially alcohol, are significantly marketed to adolescents, making them more vulnerable. My concern is that adolescents have an image that a lot of substances are benign, especially cannabis. That all gets reinforced by what they see from adults or in movies and through other media. Adolescents don’t have all the information, and they tend to progress into problematic cannabis use without even realizing that it’s possible.

 

CATR: Changing focus a little, you reminded us earlier of how we know that cannabis use can cause psychosis in some people. How prevalent do you think that is?

Dr. Gray: This appears to be something a bit more complex, and like most mental illness, there’s likely a gene-environment interplay. For example, there could be people who are genetically predisposed to a psychotic disorder, and the onset could be hastened because of heavy cannabis use in adolescence. Or, there could be no relationship between the cannabis use and the onset. There’s some debate as to whether a person who smokes cannabis is vulnerable to psychotic illness independent of genetic factors, but that remains an open question. There’s also a relationship in that those who already have an established mental health disorder seem to have higher rates of cannabis use than the general population. I don’t think it’s quite as prevalent as tobacco use with schizophrenia, but a high level of cannabis use is associated with several psychiatric disorders (Bianco C et al, JAMA Psychiatry 2016;73(4):388–395).

 

CATR: What about the common idea that cannabis use might be helpful in the treatment of some mental health disorders? What has your research shown here?

Dr. Gray: There’s been some interest in the idea of cannabis or cannabinoids as a treatment option for disorders, such as PTSD (O’Neil ME et al, Ann Intern Med 2017;167(5):332–340). There is some work on that underway, but as of right now there’s not convincing evidence of cannabis as a safe and effective treatment option for most psychiatric disorders. Research has been done tracking cannabis users over time, comparing those who have psychiatric disorders and those who don’t. Generally speaking, though, the results show that there’s more evidence that cannabis use tends to worsen the illness rather than help it (Moore TH et al, Lancet 2007;370(9584):319–328). There’s also some interesting research from the National Academies of Sciences, which shows how the jury’s still out on the therapeutic value of using cannabis. (See: http://bit.ly/2HLWhkG.)

 

CATR: So, maybe outside of PTSD, what you’re saying is that there currently is no compelling evidence showing that smoking cannabis is helpful with any psychiatric disorder?

Dr. Gray: Yes, I would say that. An important point here is that a large bulk of research on cannabinoids and therapeutics has been through oral administration of specific cannabinoids in reliable doses. Very little of that research has been on smoking cannabis. When researching pharmacotherapies in general, we prescribe a specific dose in a specific frequency of a specific chemical compound, with multiple, double-blinded studies using placebo. This isn’t necessarily applicable to smoked marijuana, because there are 66 different cannabinoids in smoked marijuana, of which THC is just one. (See: learnaboutmarijuanawa.org/factsheets/cannabinoids.htm.)

 

CATR: So, you would recommend that we tell our patients with schizophrenia, schizoaffective disorder, bipolar disorder, or those who lean toward the psychotic spectrum to definitely not smoke marijuana?

Dr. Gray: I think there’s a lot of evidence of harms. So, yes, I think within psychiatric populations, we have to be very, very concerned and recommend that our patients abstain from cannabis use.

 

CATR: And how good is the evidence that cannabis use can still be helpful as a treatment with some non-psychiatric illnesses?

Dr. Gray: There has been some very interesting work on treating refractory seizures in special populations, which seem to be responding to cannabidiol, a specific non-“high”-inducing cannabinoid compound. And for a while now, individuals with HIV/AIDS symptoms and those with nausea during chemotherapy have seen benefits from oral THC, also called dronabinol. And there’s also a combined 1:1 ratio THC plus cannabidiol oral preparation, which the FDA is looking at, for potential help with multiple sclerosis. But there’s still a lot of research that needs to be done, and there have certainly been logistical challenges with conducting this line of work.

 

CATR: Before we end, are there any final thoughts on the challenges of warning our patients about cannabis use?

Dr. Gray: Yes. I always come back to the idea that I don’t want anyone to get trapped in polarization around the issue of using cannabis. That’s a losing proposition. I think as a clinician, when you’re faced with a patient who’s a heavy cannabis user, confronting the patient about it at the outset is likely not to going to get you anywhere. I think the most important first thing to do is to understand what the patient likes about smoking marijuana, what’s driving the substance use, and what is interesting about marijuana to the patient. This could be a vehicle for more conversations around risk-benefit, and around what might be beneficial about reduction or elimination of use. Getting patients to stop using cannabis is a gradual process.

 

CATR: Thank you for your time, Dr. Gray.