Tag Archives: Cannabis and Psychosis

07/4/23

PREPARING to Legalize Cannabis

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Marijuana legalization in the US has been steadily moving forward in a piecemeal, state-by-state way for several years now. According to the National Conference of State Legislators, as of April 24, 2023 38 states and the District of Columbia have legalized cannabis products for medical use, and 22 states and the District of Columbia have legalized the recreational use of marijuana. Apparently anticipating the inevitability of legalization on a national level, Congressman Dave Joyce introduced H.R. 2598, the PREPARE (Post-Prohibition Adult Use Regulated Environment) Act on April 13, 2023, “To establish a Commission on the Federal Regulation of Cannabis to study a prompt and plausible pathway to the Federal regulation of cannabis.” Hakeem Jefferies, the Minority Leader of the House of Representatives, told Forbes: “The PREPARE Act will give lawmakers a bipartisan platform to legislate not only a fair and responsible end to prohibition but also a safer future for our communities.” However, two studies published in May of 2023 suggest that ending the so-called “prohibition” of marijuana may not be a responsible or safe action for some members of our communities.

The movement towards recreational marijuana legalization is promoted by a widespread sense that casual cannabis use is benign. However, a Columbia University study by Sultan et al, “Nondisordered Cannabis Use Among Adolescents,” found that teens who used marijuana recreationally were 2 to 4 times more likely to develop depression and suicidality than teens who didn’t use it at all. The lead study author, Ryan Sultan, said in a Columbia University press release, “We were surprised to see that cannabis use had such strong associations to adverse mental health and life outcomes for teens who did not meet the criteria for having a substance use condition.”

Their study found that adolescents with nondisordered cannabis use (NDCU) and cannabis use disorder (CUD) had increased odds of adverse psychosocial events. Both were significantly associated with adverse psychosocial events in a stepwise gradient manner. Sultan said their study was the first to identify that subclinical, nondisordered cannabis use has “clear adverse and impairing associations for adolescents.”

In line with past studies, cannabis use among adolescents was associated with greater odds of depression and suicidal ideation. These in turn were associated with long-term adverse educational and occupational attainment outcomes “and increased risk of harmful substance use in adulthood.” There was also evidence of worse executive control, decreased attention and deficits in episodic memory. Compared to nonusers, adolescents in NDCU and CUD groups were around 2-3 times more likely to experience cognitive deficits.

We observed a stepwise severity gradient for the odds of psychosocial associations among nonuse, NDCU, and CUD. This severity gradient was also observed in prevalence values for adverse psychosocial events across all degrees of cannabis use. Furthermore, this observation was corroborated by a stepwise cannabis use frequency trend between NDCU and CUD.

The researchers thought their findings were particularly concerning given the increasing popularity of marijuana as states continue to move toward making the drug legal. They concluded that with the growing acceptance of both medicinal and recreational cannabis use in the US, “clinicians should be vigilant to screen, evaluate, and treat cannabis use in adolescents.”

The second study was a huge Danish study of over 6 million people that discovered a strong association between cannabis use disorder and schizophrenia. The research team included Nora Volkow, the Director of the National Institute on Drug Abuse (NIDA). The study, “Association between cannabis use disorder and schizophrenia stronger in young males than in females,” analyzed health records spanning over 5 decades in order to estimate the fraction of schizophrenia cases that could be attributed to cannabis use disorder. A Scientific American review of the study said it found up to 30% of the schizophrenia diagnoses—around 3,000 in total—could have been prevented if men between the ages of 21 and 30 had not developed cannabis use disorder. The Scientific American review said:

The Danish epidemiology study does not offer hard-and-fast proof of the cannabis-schizophrenia connection, which could be accomplished only through randomized controlled trials. But this link is supported by the fact that marijuana use and potency have risen markedly—from 13 percent THC content in Denmark in 2006 to 30 percent in 2016—alongside a rising rate in schizophrenia diagnoses. “While this isn’t proving causality, it’s showing that the numbers behave exactly the way they should, under the assumption of causality,” says Carsten Hjorthøj, the study’s lead author and an associate professor at the Mental Health Services in the Capital Region of Denmark and the University of Copenhagen.

This study won’t resolve the long-running debate over the statistical cause-and-effect relationship between cannabis and schizophrenia. For example, David Nutt thought the research was intriguing, but it also raised more questions. He asked whether some of the cases may have been misdiagnosed with schizophrenia rather than an alternative diagnosis—like cannabis-induced psychosis. Along with the researchers, he pointed to the lack of data on the participants’ frequency of cannabis use or age of first use or the amount of THC in the products they used.

However, Robin Murray, a professor of psychiatric research at the Institute of Psychiatry at King’s College London and co-editor in chief of the medical journal Psychological Medicine said the Danish study examined specific factors more closely—gender and age—than previous investigations of the possible link between cannabis and schizophrenia. He thought it added to the growing body of research that has gradually discounted other factors to cannabis as a trigger for schizophrenia, making the connection more plausible, “So causal effect is almost certain.” For more on cannabis and schizophrenia, and Robin Murray’s own research into marijuana, see “Gambling with Cannabis and Psychosis” and “Cannabis and Psychosis: More Reality Than Satire.”

Psychiatric Times periodically published articles to educate its readers on cannabis and its association with schizophrenia. In “Cannabis Confusion” John Miller noted that he’s read numerous articles in the psychiatric literature that made conflicting conclusions about the effects of cannabis on cognition, its risk of psychosis, addictive potential, and its effects on suicidality, depression, anxiety, and pain relief. He thought there was only one consistent finding: Heavy cannabis use during brain development increases the risk of psychosis and cognitive impairment.

A likely explanation for the wide-ranging discrepancies is that cannabis is the product of a plant that is not a single molecule or pure substance. Many articles with the word cannabis in the title can be discarded as meaningless unless the authors took the additional step of testing all of the cannabis used by their study subjects for the quantitative and qualitative molecules present.

He noted that as more states legalize cannabis for medical or recreational use, it is likely that federal laws will eventually make cannabis use legal on a national level. “That will create an opportunity to require a comprehensive analysis and disclosure of all the components of the numerous strains of cannabis currently being sold in state dispensaries or on the streets.”

Fuller Torrey, a research psychiatrist specializing in schizophrenia, commented in “Is Cannabis Use Increasing Schizophrenia?” on an earlier Danish study that claimed the use of cannabis was a likely cause of the increasing incidence of schizophrenia over the past two decades. He noted that an increasing incidence of schizophrenia, or psychosis in general has also been reported in England, Switzerland and Canada. Torrey also gave citations and links to the various studies that supported his statement. He also thought the move towards legalizing recreational use in the US meant that “a possible relationship between cannabis use and increasing schizophrenia is potentially very important and needs to be confirmed.” He said:

It is an embarrassment to American medicine that NIMH has so little to contribute on such an important question. At a minimum, NIMH should issue a request for proposals to try and confirm the Danish study in another country which has appropriate data so that we will have a definitive answer to this question.

In “Does Cannabis Cause Psychosis?” Brian Miller reviewed several research studies of the relationship between cannabis and psychosis and concluded there was a robust association between cannabis use and the risk of psychosis, with evidence of a dose-response relationship, “which supports the plausibility of a causal association.”

Comorbid cannabis use is highly prevalent in psychosis (especially FEP [first episode of psychosis], with declining use over time), with strong evidence for an earlier age of onset of illness, as well as effects of psychopathology and cognition. In patients with psychosis, continued cannabis use is associated with antipsychotic nonadherence, illness relapse, and longer hospitalizations. These findings raise the possibility of a dose-response relationship between current cannabis use and transition to psychosis. Findings suggest that targeting cannabis use during the UHR [ultra-high risk] period may confer significant benefits on long-term outcomes. Continued cannabis use is also a potential target for intervention to improve antipsychotic adherence and other outcomes in patients with psychosis. Future research in this area is clearly warranted to elucidate mechanisms and novel treatment strategies for relevant populations.

Further research is needed to clarify the potential harms and adverse effects from using cannabis and marijuana products. While not yet proved conclusively, it does seem that there is a causative connection between schizophrenia and using marijuana for some people, but not for all people. Although this is more evident with heavy users (those who could be classified as having a cannabis use disorder), the Sultan et al study found there were even adverse mental health and life outcomes for teens that used marijuana, but did not meet the criteria for a substance use condition.

Cannabis use among adolescents increased the odds of depression and suicidal ideation among adolescents. Consistent with past research, there was also evidence of worse executive control, decreased attention and problems with episodic memory. When compared to nonusers, adolescents who used marijuana were 2 to 3 times more likely to experience cognitive deficits.

Heather Baccus spoke to America Reports on Fox News of how she believes her son’s marijuana use led to his psychotic break a few months before he committed suicide in July of 2021. Randy began using marijuana when he was 15 and had a cannabis user disorder within a year. By the time he was 21, he was experiencing delusions and paranoia. Heather said he thought it was helping him with his anxiety and depression, which she said he did not have until after he began using marijuana.

He knew that he would manage and function fairly well in life, but he was paranoid. He thought his roommates were out to get him. He thought that people at work were out to get him. He would quit a job quickly. He accused one of his employers of being in the mob. When he had a full-blown attack in March of 2021, he called us and said the mob was coming after him, that they were coming after us, and he just was out of sorts.

There is a video clip of a short interview with Nora Volkow, the director of NIDA and a coauthor of the above cited Danish study in the Fox News article. She said marijuana is not as benign as we would like it to be and is associated with psychosis. “High doses, regular use can be harmful.” She said there were likely three possibilities. Marijuana use triggers an episode in some individuals that have a latent risk for psychosis. In others, it may just accelerate the timing of the psychosis. Finally, it may also trigger a psychotic event that would not otherwise happen.

The PREPARE Act sounds like a responsible, proactive step to take before we move towards national legalization of marijuana. But I don’t believe we are thinking about the concurrent increase with adverse mental health concerns like depression, suicidal ideation and psychosis. What do we need to do to PREPARE for that?

03/31/20

Cannabis and Psychosis: More Reality Than Satire

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On December 19, 2014, in Cairns Australia Raina Thaiday stabbed eight children to death. She was related to all the children. “Seven of the kids were hers. The eighth was her niece.” On April 6, 2017, a Justice of the Supreme Court of Queensland heard testimony from Thaiday’s psychiatrists and later determined she couldn’t control her actions and had broken from reality when she killed her children. “In medical terms, she suffered from psychosis and the devastating mental illness schizophrenia, which can cause hallucinations, delusions, and paranoia.” Justice Dalton ruled that marijuana had caused her mental illness.

“Thaiday gave a history of the use of cannabis since she was in grade 9,” Dalton wrote. “All the psychiatrists thought that it is likely that it is this long-term use of cannabis that caused the mental illness schizophrenia to emerge.” With those words, Dalton made one of the first judicial findings anywhere linking marijuana, schizophrenia, and violence—a connection that cannabis advocates are desperate to hide.

The above anecdotal story was described in Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence, by Alex Berenson. He noted the association of cannabis and violence dated back to around 100 AD. A Chinese pharmacopeia called the Pen-ts’ao Ching, warned how cannabis “stimulate(d) uncontrollable violence and criminal inclinations.” More recently, in 2017 the National Academy of Medicine issued a research report titled, “The Health Effects of Cannabis and Cannabinoids.” The report concluded there was substantial evidence of an association between cannabis use and the development of schizophrenia or other psychoses. And the highest risk was among the most frequent users.

The association between cannabis use and the development of a psychotic disorder is supported by data synthesized in several good-quality systematic reviews. The magnitude of this association is moderate to large and appears to be dose-dependent, and it may be moderated by genetic factors. Factors contributing to the strength of the evidence derived from the cited systematic reviews include large sample sizes, the relative homogeneity of the findings, the presence of relationships between the dose/exposure and the risk, the studies having been controlled for confounders, and the systematic reviews having assessed for publication bias. The primary literature reviewed by the committee confirms the conclusions of the systematic reviews, including the association between cannabis use and psychotic outcome and the dose-dependency of the effects, further bolstering the overall strength of evidence for our conclusions.

Cascading social changes, with state-after-state legalizing medical and then recreational marijuana has broadened its use beyond the subculture of jazz musicians who smoked it in the 1920s and 1930s. Berensen noted the number of emergency room visitors diagnosed primarily with psychosis and secondarily with marijuana-related problems tripled between 2006 and 2014 from 30,000 to 90,000. “By 2014, 11 percent of Americans who showed up in emergency rooms with a psychotic disorder also had a secondary diagnosis of marijuana misuse.” Studies from Denmark and Finland have shown recent increases in schizophrenia diagnoses coming after rising cannabis use. The authors of the Denmark study said: “The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use.”

Marijuana is an intoxicant that can disinhibit users, too. And though it sends many people into a relaxed haze, it also frequently causes paranoia and psychosis. Sometimes those are short-term episodes in healthy people. Sometimes they are months-long spirals in people with schizophrenia or bipolar disorder.

There is also a correlation between marijuana and violence, despite the denial of marijuana proselytizers. All four states that legalized marijuana in 2014 and 2015—Alaska, Colorado, Oregon and Washington—have seen sharp increases in murders and aggravated assaults. The four states combined have an increase in murders of 25% and an increase in assaults of 35% between 2013 and 2017. That compares nationally to an increase in murders of 20% and in aggravated assaults of 10%. There is only an association here; it is correlative, not causative. “Knowing exactly how many of these crimes are related to marijuana is impossible without researching each of them in detail, but police reports and arrest warrants show a clear connection in many cases.”

There is also a genre of scholarly studies linking marijuana and psychosis. Jim van Os, a Dutch psychiatrist and epidemiologist was the lead author of a 2002 study, “Cannabis use and psychosis: A longitudinal population-based study,” that found a history of cannabis use increased the risk of a follow-up psychosis outcome for subjects with no history of psychosis. “A baseline lifetime history of cannabis use was a stronger predictor of psychosis outcome than was use over the follow-up period and use of other drugs.” There was an additive interaction between cannabis use and the risk of psychosis. “The difference in risk of psychosis at follow-up between those who did and did not use cannabis was much stronger for those with an established vulnerability as baseline than for those without one.” Berensen said Os’s survey of Dutch adults indicated adult users of marijuana were far more likely to develop psychosis than nonusers.

Benjamin Murrie and others did a study of the proportion of people with substance-induced psychoses who transition to schizophrenia. They found that the rate of transition to schizophrenia was higher after cannabis-induced psychosis (34%) than other substance-induced psychoses, including amphetamines (22%) and hallucinogens (24%). Their study found that substance-induced psychoses (especially cannabis-, hallucinogen- and amphetamine-induced psychoses) are associated with a significant risk of a later diagnosis of schizophrenia. And that risk is “only slightly less than that observed for some other brief psychotic episodes.”

Commenting on the study for Psychiatric Times, Brian Miller said the study’s findings have important implications for mental health services. Substance-induced psychoses are common reasons for individuals to seek help. Additionally, they are associated with a substantial risk of transition to schizophrenia. He said a key implication of the findings is that treating cannabis-, amphetamine-, and hallucinogen-induced psychoses should be considered in the same framework of intervention as other brief psychotic disorders, and may help decrease the rates of transition to schizophrenia.

Sir Robin MacGregor Murray and Marta Di Forti, leading experts on cannabis and psychosis, were part of a team of researchers in a study of first-episode psychosis attributable to the use of high potency cannabis, or “skunk.” Compared to those who never used cannabis, individuals who used skunk were nearly twice as likely to be diagnosed with a psychotic disorder if they used less than once per week, almost three times as likely if they used skunk weekends, and more than five times as likely if they were daily users. In a Reuters article on the study, Murray said: “Fifteen years ago, nobody thought that cannabis increased the risk of psychosis… But now the evidence is pretty clear.”

The results of our study support our previous conclusions from analysis of part of the sample; use of high-potency cannabis (skunk) confers an increased risk of psychosis compared with traditional low-potency cannabis (hash). Additionally, because of the increased sample size in the present study, we were able to combine information on frequency of use and type of cannabis used into a single measure. This combined measure suggested that the strongest predictor of case-control status (ie, predictor of whether a random individual would be case or control) was daily-skunk use.

Even the founder of NORML, Keith Stroup, knew that when marijuana was potent enough to get him high, it could make him paranoid. In his 1981 book, High in America, Patrick Anderson related how onetime Stroup “rocked so obsessively in a rocking chair that the chair broke.” Then he became convinced someone was about to murder his new daughter and raced home to save her. Another time after smoking pot, he became convinced that a friend who had come for dinner was going to kill them.

Case reports connecting marijuana and psychosis began appearing in the 1970s, as cannabis use surged. There was “Psychotic symptoms due to cannabis abuse,” in the National Library of Medicine, 1970; “Forty-six cases of psychosis in cannabis abusers,” in International Journal of the Addictions, 1972; “Psychotic reactions following cannabis use in East Indians,” in Archives of General Psychiatry, 1974. “Cannabis-associated psychosis with hypomanic features” appeared in Lancet in 1982. But these were only case reports.

Sven Andréasson was able to demonstrate a statistical link between marijuana and schizophrenia for the first time in, “Cannabis and schizophrenia: A longitudinal study of Swedish conscripts,” Lancet, 1987. Andréasson did a follow up study to examine if people who developed schizophrenia after smoking marijuana were different than schizophrenic patients who had never smoked, “Schizophrenia in users and nonusers of cannabis,” Acta Psychiatrica Scandinavica, 1989. Berenson reported Andréasson found that marijuana smokers tended to be relatively high-functioning before their illness, while nonsmokers had a more classic history representative of schizophrenia—they were troubled from a much younger age.

Based on his data and later findings, Andréasson says he believes that cannabis is responsible for between 10 percent and 15 percent of schizophrenia cases. Few people develop schizophrenia solely because of smoking, he thinks. But many who would not have become sick do so because marijuana pushes their vulnerable brains over the edge.

Then there was a longitudinal study of individuals from Dunedin, New Zealand: “Cannabis use in adolescence and risk for adult psychosis,” in the British Medical Journal, 2002. The authors found cannabis use in adolescence increased the likelihood of experiencing symptoms of schizophrenia in adulthood. Individuals who used cannabis by the age of 15 were 4 times as likely to have a diagnosis of schizophreniform (a psychotic illness with schizophrenia-like symptoms lasting less 6 months). Their findings agreed with the Andréasson study, and added three new pieces of evidence.

Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding. Thirdly, risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression.

Along with the van Os study, described above, the Andréasson study and the Dunedin study provide significant and powerful evidence linking cannabis and mental illnesses, such as schizophrenia and depression. They all reached the same conclusion, came at the question of marijuana and psychosis from three different directions and were from three different countries. An editorial in the BMJ, “Cannabis and mental health,” discussing these three studies said:

Although the number of studies is small, these findings strengthen the argument that use of cannabis increases the risk of schizophrenia and depression, and they provide little support for the belief that the association between marijuana use and mental health problems is largely due to self-medication.

The connection between marijuana and madness harkens back to an education-exploitation film called Reefer Madness or Tell Your Children. Reefer Madness is a melodramatic, 1936 film that attempted to show the dangers of marijuana use. It became a satirical favorite among advocates for marijuana reform in the 1970s when it was used in an attempt to raise support for the California Marijuana Initiative in 1972. Keith Stroup found a copy in the Library of Congress archives and bought a print for $297. Robert Shaye of New Line Cinema saw the film, realized it was in the public domain, and began distributing the film nationally.

In the film, Ralph, who is a dealer, becomes paranoid from his use of marijuana (and he also accidentally killed a teenaged girl). The Boss eventually sends someone to kill Ralph, who struggles with the hitman and beats the assassin to death with a stick. Ralph is then arrested and sent to an asylum for the criminally insane, “for the rest of his natural life.” The connection between marijuana and madness seems to becoming less campy satire and more reality. For more on the film, see “Remembering Reefer Madness.”

06/30/14

Is Legalizing Reefer Madness?

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The Pew Research Center found that for the first time since 1969, more Americans favor legalizing the use of marijuana (52%) than those who oppose it (45%). The change started after 1991, when 78% of Americans opposed legalization and merely 17% supported it. The greatest support for legalization was found within youngest age group, individuals born since 1980. Sixty-Five percent of these Millennials favor legalizing marijuana.

The past three years have seen a rapid shift in support of legalization. In 2010 only 41% were in support of legalization. “Since then, support for legalization has increased among all demographic and political groups.” Boomers, born between 1947 and 1964, have seen their support for legalizing marijuana increase from 24% in 1994 to 50% in 2013.

Along with the increased support for marijuana legalization, there has been a corresponding decline in negative attitudes about marijuana. Currently, 32% believe that smoking marijuana is morally wrong, an 18 point decline since 2006 (50%). Over that same period, the percentage of people who said that smoking marijuana was not a moral issue rose 15 points from 35% in 2006 to 50% in 2013.

Over the past three decades, attitudes on whether or not marijuana was a gateway drug have shifted as well. A 1977 Gallup survey found that 60% of people believed that marijuana was a gateway drug. In 2013, only 38% believed so. Most of this shift is the result of generational change. Gen X and Millennials were far less likely to say that marijuana use leads to the use of hard drugs (36% of Gen X and 31% of Millennials).

The efforts of organizations like NORML and the Marijuana Policy Project seems to be paying off. They have been working to “legalize the responsible use of marijuana,” so that marijuana is “legally regulated similarly to alcohol.”

But I wonder if the momentum towards legalization is moving in right direction. NORML and the Marijuana Policy Project cited various studies on the safety profile of cannabis, the therapeutic potential of cannabis and how long-term cannabis use does not cause permanent cognitive impairment. But there seems to be an opposing consensus on the potential harmful effects of marijuana use.  Just a few of these concerns are noted below.

  • The potency of marijuana has doubled since 1998; tripled in the past 20 years.
  • In 2010, marijuana was involved in more than 461,000 ER visits nationwide.
  • In 2011 around 872,000 individuals received treatment for marijuana use.
  • In 2012 4.3 million individuals could be diagnosed as dependent upon or abusing marijuana.

There is also clear evidence of an association between marijuana use and psychosis. NORML gave a summary of the 1995 Lancet study that said smoking cannabis, even long-term use, was not harmful. Yet they ignored the Lancet’s retraction of that support published in the July 2007 edition of the Lancet:

In 1995, we began a Lancet editorial with the since much-quoted words: “The smoking of cannabis, even long term, is not harmful to health.” Research published since 1995, including Moore’s systematic review in this issue, leads us now to conclude that cannabis use could increase the risk of psychotic illness. Further research is needed on the effects of cannabis on affective disorders. The Advisory Council on the Misuse of Drugs will have plenty to consider. But whatever their eventual recommendation, governments would do well to invest in sustained and effective education campaigns on the risks to health of taking cannabis.

A web site, Cannabis & Psychosis, was recently launched to “increase awareness and understanding of the relationship between cannabis use and psychosis from the perspective of youth.”

Public support for the legalization of marijuana is growing. The potency of marijuana is increasing. And the evidence for the harmful effects, especially psychosis and other mental health issues is becoming clearer. Marijuana will likely surpass alcohol and tobacco as a public health concern once it is legalized. For more information on the health concerns with marijuana go to “Marijuana Research Findings” on this website.