CCPR: Tell us a little bit about your background.
Dr. Gobbi: I trained in medicine, psychiatry, and psychotherapy in Rome, Italy, then received a PhD in neuroscience, working in preclinical psychopharmacology. I now work in our mood disorder clinic and ER, and I direct our basic psychopharmacology lab (neurobiological psychiatry unit), including research on cannabis and the endocannabinoid system. I wear two hats: clinician and basic researcher.

CCPR: What are your thoughts about the relationship between depression and cannabis use in adolescents and young adults?
Dr. Gobbi: The relationship is complex and goes two ways. About 50% of adolescents with depressive symptoms smoke cannabis, most likely for self-medication reasons, yet recreational cannabis can increase the risk of depression. In our recent meta-analysis, we looked at the association between adolescent cannabis consumption and depression in young adulthood and found an increased risk of about 40%. Some research says that young people who are depressed and smoke cannabis can develop treatment-resistant depression (Goldstein BI et al, J Am Acad Child Adolesc Psychiatry 2009;48(12):1182–1192). We also found a link between cannabis consumption in adolescents and suicidality, about a 50% increase (Gobbi G et al, JAMA Psychiatry 2019;76(4):426–434). So cannabis consumption may trigger depression, even in the absence of a premorbid depression or predisposition for depression.

CCPR: How does this inform our assessment of patients? What do you recommend for an everyday clinician to sort all this out?
Dr. Gobbi: Very often the symptoms of cannabis withdrawal and the symptoms of chronic cannabis consumption (or cannabis use disorder [CUD]) overlap with those found in depression. It is important for doctors to try to sort out the symptomatology of depression, but also to assess the patient’s cannabis consumption—both past and current.

CCPR: What types of questions should we be asking?
Dr. Gobbi: Try to establish when cannabis use first started—at what age and under what circumstances. How often does the patient use cannabis: weekly, monthly, or every day? This is important since there are serious mental health consequences from both daily as well as weekly consumption of cannabis (Silins E et al, Lancet Psychiatry 2014;1(4):286–293). THC—the main component of cannabis—and its metabolites have a long half-life, up to 2 weeks. So, even if somebody smokes only once a week, the cannabis is still present in the body and in the brain (Huestis MA, Handb Exp Pharmacol 2005;(168):657–690). You’ll also want to ask how much cannabis the patient consumes and what the concentration of THC is, if the patient knows.

CCPR: We’ve all heard that the THC concentration is higher now than it used to be.
Dr. Gobbi: Right. Over the last several years the concentration of THC has risen dramatically. One study in the US had it at 4% in 1995 and 12% in 2016 (ElSohly MA et al, Biol Psychiatry 2016;79(7):613–619). Recreational cannabis has been legal in Canada since October 2018; there, legal shops sell cannabis concentrations with 20%–30% of THC, which is a pharmacologically significant concentration. In the illegal market, THC concentrations in joints can range from 10% to 50%. The statistics we have are mostly from epidemiological studies done in the 1980s, 1990s, and early 2000s, and we worry what will happen to people who are smoking cannabis with today’s higher THC concentrations.

CCPR: What about other types of cannabis?
Dr. Gobbi: Hashish, or butane hash oil—also called BHO, budder, crumble, dabs, earwax, errl, honeycomb, honey oil, live resin, oil, or wax—may have very concentrated THC, about 60%–70%. A new trend is also edible cannabis—cookies, candies, etc—that can contain up to 10 mg of THC per serving (Source: Health Canada).

CCPR: Besides how often and how much cannabis, what else we should be asking?
Dr. Gobbi: Find out why the patient is using it. Patients often report consuming cannabis to self-medicate their depression, anxiety, insomnia, or pain, and also for improving socialization skills. When patients with depression see a psychiatrist in a mood disorder clinic, they aren’t making the connection that their depression could be caused by cannabis or that cannabis can worsen their depression.

CCPR: So, what do we do? Do we use motivational interviewing, or harm reduction, to try to get them to use just a little bit less?
Dr. Gobbi: After asking patients about their level of consumption of cannabis, the next step is to motivate and teach them about the possible consequences of cannabis. This can take a long time. Some patients accept this slowly through motivational therapy. Some agree to slowly decrease consumption of cannabis or stop completely, and other patients deny the problem. One of the complications of CUD is that patients underestimate the impact of cannabis consumption on mental health, so it’s not always easy to motivate patients with depression to stop their cannabis use. However, motivational therapy is an evidence-based approach, as is cognitive behavioral therapy to stop the use of cannabis. (Editor’s note: For more about motivational therapy, see the Q&A with Dr. D’Amico in this issue.)

CCPR: How do you assess if a patient has CUD? How do you recognize the symptoms of withdrawal?
Dr. Gobbi: The symptoms of cannabis withdrawal overlap with the symptoms of depression: namely mood changes, diminished appetite, irritability, and insomnia. Patients also can have headaches, loss of focus, sweating, chills, an increased feeling of depression and paranoia, as well as stomach problems. It is difficult for both the clinician and the patient to definitively say which symptoms come from depression and which come from cannabis withdrawal. Sometimes, by developing a close relationship with the patient, you can better understand the delineation. For example, if a patient on a stable antidepressant treatment starts suffering from insomnia, increased irritability, and sweating a week after stopping cannabis, these symptoms are more likely linked to cannabis withdrawal than depression. At this point, it is mandatory to motivate the patient to stop cannabis completely and use medications to relieve withdrawal symptoms.

CCPR: What do we do about people who continue to use weed?
Dr. Gobbi: There are no medications that are FDA labeled for treating CUD, but there are some medications that we use off-label. In our department, one of the most accepted treatments is the use of gabapentin. There are some clinical trials showing that gabapentin can treat CUD (Mason BJ et al, Neuropsychopharmacology 2012;37(7):1689–1698). There is also evidence for the use of lithium and valproic acid, as well as bupropion, venlafaxine, and buspirone (Lee DC, Drug Alcohol Depend 2019;194:500–517).

CCPR: Those are interesting choices. Some people use topiramate as an off-label approach. Do you ever consider that?
Dr. Gobbi: Yes, topiramate also has some evidence. And all the mood stabilizers can also help in CUD. As I mentioned, there can also be uses for gabapentin, lithium, and valproic acid. All these drugs are used off-label, and patients and families need to know this.

CCPR: Some people seem to get addicted to gabapentin. Have you seen that? Is that something we should be worried about?
Dr. Gobbi: No. We frequently use gabapentin here, and that hasn’t been my experience. When people stop gabapentin, they may feel more anxious, but to the best of my knowledge, it is more a decrease in the medication (gabapentin) that was controlling the anxiety, not a real addiction.

CCPR: What about direct medication treatment of underlying depression or anxiety disorders?
Dr. Gobbi: Current scientific evidence suggests that patients with comorbid depression and CUD should be treated with mood stabilizers (gabapentin, valproate, lithium) as well as antidepressants (bupropion, SSRIs, SNRIs), and there are several theories why this can help with CUD. Interestingly, a recent clinical study by D’Souza and colleagues found that fatty acid amide hydrolase (FAAH) inhibitor worked to treat the withdrawal symptoms and the mood symptoms, but also the craving for cannabis by stopping the breakdown of endocannabinoids in the brain (D’Souza DC et al, Lancet Psychiatry 2019;6(1):35–45).

CCPR: That’s really interesting.
Dr. Gobbi: Yes, and very important. This study opens further avenues for the treatment of CUD. Also, synthetic THC (nabilone) may reduce cannabis withdrawal, but not cannabis consumption (Haney M et al, Neuropsychopharmacology 2013;38(8):1557–1565).

CCPR: Good to know. So many people ask about CBD. We certainly have a lot of people who are purchasing and using it, even though we might not think it’s a great idea. What do you think about the safety of CBD?
Dr. Gobbi: CBD is worrisome for two reasons. First, people sometimes try CBD for bipolar disorder or depression rather than opting for a first-line treatment—so they bypass effective treatment. The other problem is that CBD’s side effects include depression and suicidality as well as interactions with any drugs or medicines that the person is already taking (see www.tinyurl.com/y6zfpbj7).

CCPR: What about the idea that CBD can be a good alternative to cannabis, in the sense that it is less likely to lead to CUD?
Dr. Gobbi: Unfortunately, we don’t have good clinical trials using CBD for CUD. Moreover, people often buy CBD on the open market that contains a percentage of THC. We would need randomized, double-blind clinical trials to really demonstrate that cannabidiol could be a good alternative to cannabis.

CCPR: Any final thoughts?
Dr. Gobbi: It is difficult for doctors and patients to recognize cannabis withdrawal. It is not like alcohol withdrawal where the patients experience clear symptoms such as tremors, headache, or vomiting in the 24 hours after the last drink. Clinicians need to remember that patients in cannabis withdrawal have “softer” symptoms, such as increased irritability, depression, headache, sweating, and loss of appetite, which can appear 1 or 2 weeks after the last joint. Often neither patients nor doctors make this connection. I want to emphasize that, although it is not so easy to evaluate, if clinicians are more aware of cannabis withdrawal, there is a better chance that they will be able to recognize and clarify how to proceed with patients.

CCPR: Thank you for your time, Dr. Gobbi.