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A CNN article titled Marijuana abuse by youth with mood disorders linked to suicide attempts, self-harm and death, study finds by By Sandee LaMotte recently reported on a JAMA Pediatrics article titled: Association of Cannabis Use With Self-harm and Mortality Risk Among Youths With Mood Disorders. This article was immediately re-posted all over the internet. As I will demonstrate, this JAMA article uses some truth to craft a disputable conclusion. In this article, I will present simple science that reveals the answer to this charge. In the CNN report, we read:

“Heavy use of marijuana by teens and young adults with mood disorders -- such as depression and bipolar disorder -- is linked to an increased risk of self-harm, suicide attempts and death, a new study has found.”

First of all, we will discover that “heavy use” is not only tracked in this study, but any use of cannabis. Sporadic, irregular use is cited as a “cannabis user.” The CNN article also highlighted three additional studies that appear to make this correlation. An analysis of these studies demonstrate the flaw to these conclusions. Teens who developed these problems with bipolar disorder later in life used cannabis. This fact becomes almost meaningless, because bipolar disorder is likely genetic, and alcohol use has also been cited as a cause:

“Bipolar disorder and alcoholism commonly co–occur. Multiple explanations for the relationship between these conditions have been proposed, but this relationship remains poorly understood. Some evidence suggests a genetic link. This comorbidity also has implications for diagnosis and treatment. Alcohol use may worsen the clinical course of bipolar disorder, making it harder to treat.” (Bipolar disorder and alcoholism )

If alcohol use in teens, and adults is linked to bipolar disorder, how can these studies single out cannabis? Ask yourself: what percentage of these teens use cannabis exclusively? Everyone knows that percentage is low. Alcohol is usually the first intoxicant teens experience, usually years before cannabis. This simple fact can explain how the conclusion of these studies are skewed, even if somewhat valid. There is a reason cannabis could cause this depression among people with these mental conditions, yet not as as a direct cause. As you continue to read, this fact will become self-explanatory. Of the three additional studies cited by this article, the first is a study that incorrectly cites a study of “same sex twins”:

“A study of adult same-sex twins found those who were dependent on marijuana were nearly three times more likely to attempt suicide than their twin who was not dependent on weed.”

Instead of a study on twins, the article links to a study of over 2,000 Norwegians. The abstract reads:

“Data were gathered through the Young in Norway longitudinal study, in which a population-based sample of 2033 Norwegians were followed up over a 13-year period, from their early teens to their late twenties. Data were gathered on: (a) exposure to cannabis use; and (b) depression, suicide ideation and suicide attempts...When adjusting for confounders, the OR was 2.9 (95% CI 1.3-6.1) for later suicide attempts in the group who had used cannabis 11+ times during the past 12 months.” (Does Cannabis use lead to Depression and Suicidal Behaviours? A Population-based Longitudinal Study)

This study has a serious flaw, and in this flaw, we discover the likely reason that cannabis use can cause depression, and suicidal thoughts. We read:

“When adjusting for confounders, the OR was 2.9 (95% CI 1.3-6.1) for later suicide attempts in the group who had used cannabis 11+ times during the past 12 months.”

The criteria of this study demonstrates a serious flaw in it's methods, but also a likely reason cannabis use can cause depression in people with bipolar disorder. People were included in this sample that used cannabis at least once a month, or as few as eleven times a year. Including extremely casual users in this sample makes it much larger, and skews the results. Maybe these people also at cheese cake once a month. A honest sample would examine bipolar patients that used cannabis at least twice a week. But even that could skew the results, but for a completely different reason I will explain. In fact, the only way to study the effect of cannabis on bipolar disorder is to study a sample of daily users.

Cannabis as a Possible Treatment for Bipolar disorder

The CNN article fails to mention several studies where cannabis is a possible treatment for bipolar disorder. For instance:

“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder. Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs. One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium's side effects.” (The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research)

“There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.” (Medicinal Cannabis for Psychiatric Disorders: A Clinically-focused Systematic Review)

“Studies exist that demonstrate that THC is an effective treatment for bipolar disorder for some. This appears to conflict with studies that correctly indicate that cannabis use can cause depression in people with bipolar disorder. There is a simple reason both of these can be true. Dopamine synthesis is elevated in people with both schizophrenia and bipolar disorder.” (Elevated Dopamine Synthesis Capacity Observed in Both Bipolar and Schizophrenia)

“Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment.” (Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood)

THC at first use elevates dopamine response, which could trigger a bipolar or schizophrenic episode, among those with these diseases. However, after this, dopamine synthisis is decreased:

“From the outset it was clear that THC exerts complex effects on the dopamine system. Early in vitro studies in rodents using radiolabelled dopamine in synaptosomes found that THC caused increased dopamine synthesis and release. However, the effects on dopamine uptake yielded conflicting results, with evidence of both increases and dose-dependent decreases. Subsequently biphasic and triphasic effects of THC were discovered, whereby low doses of THC produced increases in the conversion of tyrosine to dopamine, but high doses of THC resulted in decreased dopamine synthesis. Likewise, complicated temporal relationships between THC administration and changes in dopamine levels were observed, such that repeated dosing results in behavioural and neurochemical tolerance –highly pertinent to the mechanisms of dependence to the drug.” (The Effects of Δ9-tetrahydrocannabinol on the dopamine system)

Higher doses of THC blunt dopamine response, which is higher among schizophrenics. Therefore, the assertion in this article that higher levels of THC cause depression among this group is wrong. Instead, THC becomes a treatment for bipolar disorder and schizophrenia. THC blunts dopamine response, as other medications that treat these illnesses. But as withdrawal from prescription medications, sudden withdrawal from cannabis can cause a “rebound” leading to depression, and thoughts of suicide. Withdrawal from Prescription Medications If cannabis use is a treatment for mood disorders, as these studies claim, this explains how the patient could haphazardly cease prescription medications, causing a “rebound.” Studies show cannabis users have less medication compliance:

“Bipolar in- and outpatients (N = 3459) were enrolled in an observational study. The influence of cannabis exposure on clinical and social treatment outcome measures was examined over the course of 1 year, as well as the effects on these associations of third mediating variables. Over 12 months of treatment, cannabis users exhibited less compliance and higher levels of overall illness severity, mania, and psychosis compared with nonusers.” (Does Cannabis Use Affect Treatment Outcome in Bipolar Disorder?: A Longitudinal Analysis)

“Non compliance” of medications in many circumstances means quitting abruptly. This would cause an increase in depression, and suicidal thoughts. This fact also confabulates the relationship proposed in this article, and in the studies cited. For instance, consider one medication used to treat these conditions, Lithium: “The authors review the studies on discontinuation of lithium therapy in terms of subsequent relapse or possible withdrawal symptoms. Withdrawal symptoms following lithium discontinuation including heightened anxiety, sleep disturbances and irritability remain controversial. Relapse of the primary illness following lithium discontinuation is a well documented serious complication.” (Lithium discontinuation: Withdrawal or relapse?)

Lithium, and other drugs used to treat bipolar disorder can cause these same depressive, suicidal thoughts upon abrupt withdrawal. Physicians can talk about “medication compliance,” but if these drugs cause side effects, common sense says that many patients will stop them. As Cannabis, Lithium inhibits dopamine response:

“...lithium modulates neurotransmitters. It inhibits excitatory neurotransmitters such as dopamine and glutamate, and promotes GABA-mediated neurotransmission.” (Lithium's Mechanism of Action: An Illustrated Review)

Both Cannabis and Lithium blunt dopamine response. This is how they can treat this illness. Therefore sudden withdrawal from either of these medications will cause depression, and suicidal thoughts! Neither should either of these medications should be used “once a month” or “twice a week.” If Lithium were used in this manner, all kinds of problems would occur. Cannabis is no different. In the second study cited by this CNN article, cannabis is singled out, and other causes ignored. We read:

"Another study of 1,463 suicides and 7,392 natural deaths in the United States found a link between any use of marijuana by adults and suicide risk after adjusting for alcohol use, depression and use of mental health services.”

But what does the study actually say? We read:

“The risk factors of marijuana use, excessive alcohol use, and firearm accessibility in the last year of life increased the odds of suicide in both genders. When compared to natural deaths, depressive symptomatology was common in female suicide decedents, whereas it was only associated with older age among male suicide decedents.” (Risk factors for male and female suicide decedents ages 15-64 in the United States. Results from the 1993 National Mortality Followback Survey)

This study does not demonstrate a link between marijuana use and suicide risk, but a link between alcohol, cannabis, and firearms! The CNN article presents a stinging rebuke of cannabis, but instead we discover that alcohol is also included in the survey. What does the data say about alcohol, and suicide risk? We read:

“People with alcoholism are up to 120 times more likely to commit suicide than those who are not dependent on alcohol.” (The Relationship Between Alcoholism and Suicide)

So, the study cited includes alcohol, which increases suicide risk. It is not only about cannabis. If alcohol rises the suicide risk this high, we could also include coffee in the next study, and arrive at the conclusion coffee leads to suicide risk, even though coffee has zero effect. Of course, there is a reason cannabis use could increase these odds: sporadic use. Because cannabis blunts dopamine response, cession can cause a dopamine “rebound” as Lithium. After this, CNN cites a third study is cited:

“And there was an increased risk of suicide for both men and women who were dependent on marijuana, according to four-year study of 6,445 Danish adults.”

However, we discover that that a key “predictor of death,” was excluded in this study:

The aim of the study was to determine excess mortality associated with cannabis use disorders. Individuals entering treatment for cannabis use disorders were followed by use of Danish registers and standardized mortality ratios (SMRs) estimated. Predictors of different causes of death were determined. A total of 6445 individuals were included and 142 deaths recorded during 26,584 person-years of follow-up. Mortality was predicted by age, comorbid use of opioids, and lifetime injection drug use. For different causes of death the SMRs were: accidents: 8.2 (95% CI 6.3-10.5), suicide: 5.3 (95% CI 3.3-7.9), homicide/violence: 3.8 (95% CI 1.5-7.9), and natural causes: 2.8 (95% CI 2.0-3.7). Following exclusion of those with secondary use of opioids, cocaine, amphetamine, or injection drug use, SMRs for all causes of death remained significantly elevated except for homicide/violence. The study underlines the need to address mortality risk associated with cannabis use disorders." (Mortality following treatment for cannabis use disorders: predictors and causes)

The drugs excluded in this sample: opioids, and injected drugs. The drug that was not excluded: Alcohol. And as we have read, there is a 120 times greater risk for suicide with alcohol use. How many of these Danish people used alcohol? This is only one possible confounding factors to using this data to blame cannabis alone for these statistics. This study does not address whether these people continued to use cannabis monthly, weekly, or daily. If they were in treatment for “cannabis use disorder,” it makes sense that they quit. Blaming cannabis years after cessation for a higher mortality when other factors-- such as alcohol use-- are excluded, is skewed science. People with bipolar disorder or schizophrenia can have their illnesses “set off” by first time cannabis use, because it initially raises dopamine levels. After this, it blunts dopamine response, which provides a treatment for these illnesses. Lithium has the same effect. Yet as Lithium causes a “rebound” if stopped abruptly, the same is true with cannabis. So, erratic use of THC, can cause the depression, and suicidal thoughts cited in this article among people with bipolar disorder, but not when used on a daily basis-- as any drug that can treat these conditions.

Russell Redden

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