Tag Archives: psychosis

08/2/22

The Future of Marijuana Legalization in Pennsylvania

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The World Drug Report for 2021 reported that roughly 200 million people used cannabis in 2019, roughly 4% of the global population. North America has the highest number of cannabis users, with an estimated 14.5% of its population use in 2019. The percentage of THC (∆9-THC), the main psychoactive ingredient in cannabis, rose from around 4% in 1995 to 16% in 2019. Although THC is responsible for the development of mental health disorders in long-term, heavy cannabis users, the percentage of adolescents who view regular cannabis use as harmful has decreased by as much as 40% during the same time period. While the potency of cannabis has increased four-fold since 1995, fewer young people see it as harmful.

Such a mismatch between the perception and the reality of the risk posed by more potent cannabis could increase the negative impact of the drug on young generations. Scientific evidence has demonstrated the harm to health caused by regular use of cannabis, particularly in young people. Evidence from surveys suggests a link between a low perception of risk and higher rates of usage. This is the case not only in Europe and the United States, but also in other parts of the world.Aggressive marketing of cannabis products with a high Δ9-THC content by private firms and promotion through social-media channels can make the problem worse. Products now on sale include cannabis flower, pre-rolled joints, vaporizers, concentrates and edibles. The potency of those products varies and can be unpredictable – some jurisdictions where cannabis use is legalized set no limit on THC content – and may be a public health concern.

(See the following charts from the World Drug Report for 2021)

In 2020, 14.6% of high-school students reported past-month use of cannabis. There was a significant increase in the daily or near-daily use of cannabis in the past two years (20919 and 2020). The daily or near-daily use of marijuana was estimated at 4.1% among high-school students in 2020, compared with almost 1% in 1991. In the past few years, the debate about medical marijuana and measures allowing for the non-medical use of cannabis in the United States have led adolescents to perceive cannabis as less harmful than was true in the past.

In the United States, the decreasing perception of risk from occasional or regular use of cannabis is considered to be a spillover effect as debates over measures allowing the medical and non-medical use of cannabis in the states considering those measures extend to other states, and the result of an increase in regular cannabis use, which comes to be perceived as less risky among users, as well as media coverage of the medical use of various cannabis products in many states containing claims of the medical benefits of cannabis products, including those of CBD.

Not only are there concerns for increases in mental health disorders among youth, there are other concerns with how cannabis effects young adults. Cannabis use among adolescents was found to be related to impaired cognition; showing delayed effects on self-control, working memory and concurrent effects on delayed memory recall and perceptual reasoning (ability to think and reason using pictures or visual information). So, exactly what are the risks when individuals, particularly adolescents and young adults, use marijuana? A meta-analysis published in The Lancet Psychiatry suggested the equivalent of one joint can induce psychotic and other psychiatric symptoms in healthy adults with no history of a major mental illness.

In “Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis,” the researchers their findings highlighted the acute risks of cannabis use, as “medical, societal, and political interest in cannabinoids continues to grow.” Significantly, they concluded that CBD (the second most common cannabinoid in cannabis) did not induce psychiatric symptoms; and the evidence that it moderated the induction of psychiatric symptoms was inconclusive. These effects were larger with intravenous administration than with inhaled.

Commenting on the results for Medscape, senior investigator Oliver Howes said “As clinicians, we need to be aware that the medical use of marijuana comes with a risk of inducing psychiatric symptoms, even in people with no vulnerability, and this needs to be factored into decisions to prescribe and to monitor.” Even if the symptoms are short-lived, people need to be aware of them because not only van they be distressing, but they can also affect decision-making and behavior. With regard to the failure of the researchers to find evidence that CBD moderates the psychotic effects of THC, Howes said, “I think it’s fair to conclude there’s a lack of consistent evidence that CBD is protecting against THC’s effect.” The mean age of the subjects ranged from early to late 20s.

An editorial of the study by Carsten Hjorthøj and Christine Merrild Posselt said the finding that low doses of THC can induce psychotic symptoms was “extremely worrying,” because they were similar to those found in medical marijuana. They also said there was no clear evidence that concurrent administration of CBD reduces symptoms induced by THC. “The authors failed to find any clear evidence that concurrent administration of cannabidiol (CBD) reduced these symptoms. Indeed, such an ameliorating effect was observed in only one of four included studies.”

This growing scientific consensus is not reflected in the mainstream public discourses, which have a major effect on the political agenda to decriminalise or legalise cannabis. It also appears that, in many places (eg, several US states), the first thing to be legalised is medicinal cannabis followed by increasing decriminalisation and sometimes complete legalisation of cannabis. It is thus of utmost importance that the public and politicians are informed of the most up-to-date evidence on cannabis. Adding to the state of this evidence is the systematic review and meta-analysis by Guy Hindley and colleagues in The Lancet Psychiatry. The authors demonstrate that Δ9-tetrahydrocannabinol (THC) leads to an increase in total symptoms, which was assessed in nine studies, with ten independent samples, involving 196 participants: standardised mean change in scores (assessed with the Brief Psychiatric Rating Scale and the Positive or Negative Syndrome Scale) 1·10 (95% CI 0·92–1·28, p<0·0001). The effect sizes were also large for other symptoms (including general psychiatric symptoms), and were induced even with low doses of THC, somewhat similar to the doses often seen in medicinal cannabis, which we find extremely important and worrying.

The significance of the above research findings should not be lost on Pennsylvania citizens and politicians. As the availability of cannabis increases in the state, as the potency of THC in that marijuana increases, we will see a corresponding increase of psychosis and other mental health-related problems among regular users. This is the future of marijuana legalization in Pennsylvania.

Medical marijuana has been legal in Pennsylvania since April 6, 2016. The first dispensary opened in the Pittsburgh area in Butler PA, on February 1, 2018. But medical marijuana dispensaries continue to spring up like “weeds.” The Weedmaps website indicated there were 39 dispensaries in the Pittsburgh area. Nineteen advertised they provided Curbside pickup.

John Fetterman, the current lieutenant governor of Pennsylvania, is running for the office of U.S. Senator and wants to see Pennsylvania “go full Colorado.” Its governor, Tom Wolf, has publicly supported the legalization of recreational marijuana. There has been legislation proposed by two state senators, the Adult-Use Cannabis Act, to legalize recreational marijuana in the state. See “Should Pennsylvania Go ‘Full Colorado’ With Marijuana?” Part 1 and Part 2.

05/28/19

The ADHD Fairy

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In case you didn’t know, there is a risk of psychosis when using ADHD stimulant medications, such as amphetamine (Adderall, Vyvanse) and methylphenidate (Ritalin, Concerta). A study published recently in The New England Medical Journal indicated the risk was low, with about 1 in 660 patients who used prescription stimulants diagnosed with new-onset psychosis. The lead author of the study, Dr. Lauren Moran, said the risk was low enough that she could not recommend not prescribing Adderall. “But from a public health perspective, there’s so many millions of people being prescribed these medications that it actually leads to thousands of people at increased risk of psychosis.” Using data from the CDC on ADHD, that meant in 2016 about 5,730 children between the ages of 2 and 17 who were taking ADHD stimulants would be diagnosed with new-onset psychosis.

Medscape reported Dr. Moran said the takeaway point was “that it’s really important to screen for potential risk factors.” These risk factors could include a history of bipolar or other psychiatric disorder, a family history of psychiatric illness, or use of cannabis (See: “Gambling with Cannabis and Psychosis”). “If patients have those risk factors, I would shy away from using the amphetamines. You don’t want to have two things that could potentially further increase the risk for psychosis.”

Moran noted that there are many college students in the area around McLean Hospital and that in her anecdotal experience as a psychiatrist working in a unit that treats patients with psychotic disorders, she’s “been seeing cases of young individuals coming in with psychosis” after stimulant use.

Moran said at the beginning of their study, a patient had a 50-50 chance of getting Adderall or Ritalin. But there has been a dramatic increase in Adderall prescriptions, to almost four times as many prescriptions for Adderall. In her experience, ADHD patients hospitalized for psychosis recovered in two weeks; some took as long as two months. But Moran is not suggesting ADHD medications are too dangerous to prescribe. Rather, she’s trying to raise awareness. “Physicians need to be aware of this when prescribing and people who are getting these medications from friends in college need to know this is a risk.”

Speaking to STAT News, Dr. Anthony Rostain said he did not think the results of the Moran et al. study was shocking. The package insert already warns of a small risk of psychosis with ADHD stimulant medication. “It will just simply be important to mention to people that the amphetamine-based compounds have a slightly higher risk… I think the take-home here should be that everyone should be informed when they are starting a medicine about risks like psychosis.” One of the risk factors he gave for psychosis was abusing the drugs—crushing and snorting them. So the implication is that the individuals at risk are those who abuse this medication, which is admittedly an issue on college campuses.

But is that the real problem, namely that the people at risk are those who are abusing ADHD stimulants? First let’s consider the industry ties of the two doctors cited here. Rostain has been a consultant to Arbor Pharmaceuticals, an amphetamine maker, and to Shire, which sells Vyvanse and developed Adderall; Dr. Moran reported only receiving a grant from the NIMH to investigate the risk of psychosis with prescription stimulants. Is Rostain contributing to some misdirection of the issue because of his industry ties?

Did you know that so-called “challenge studies,” where amphetamine and methylphenidate were used to instigate symptoms of psychosis, were done in the name of science? Robert Whitaker co-wrote a series of articles that described how beginning in 1972, psychiatric researchers used amphetamine, methylphenidate and ketamine “to deliberately provoke psychotic symptoms in more than 1,200 schizophrenic patients.” In some cases, the level of psychosis experienced by these patients was called “severe.” Some of these experiments were conducted by prominent researchers at the National Institute of Mental Health. David Janowsky’s work established the idea that psychosis-inducing drugs “could be used as ‘challenge agents’ to turn patients into models for studying psychotic illnesses.”

Symptom-exacerbation experiments were pioneered by Dr. David Janowsky of Vanderbilt University. In 1974, he reported success in developing a new tool for studying schizophrenia. He found that giving schizophrenic patients methylphenidate (Ritalin) caused ”a dramatic intensification of preexisting symptoms, such as hallucinations and delusions,” and that amphetamine also exacerbated their psychosis. Both drugs are known to release dopamine, a messenger chemical in the brain, and Janowsky’s experiments provided indirect evidence that the biological mechanism of psychosis involved an overactive dopamine system.

Dr. Jeffrey Lieberman, currently the department chair of psychiatry at Columbia, did several challenge studies with methylphenidate. In a 1987 study, 34 stable outpatients receiving antipsychotics were given methylphenidate and then withdrawn from their antipsychotics. Three weeks later, they were given another infusion of methylphenidate. They were then followed up for 52 weeks or until they relapsed—in other words until their symptoms returned.

In a 1990 study, 38 patients who met the criteria for schizophrenia or schizoaffective disorder were given methylphenidate. These were patients experiencing their first acute psychosis. The methylphenidate produced an increased psychopathology seen in the worsening of their symptoms. And in a 1987 article, Lieberman and his coauthors commented that methylphenidate appeared to have a greater “psychotogenic potency” than amphetamine. They hypothesized there was a subgroup of schizophrenic patients who exhibited psychotic activation with psychostimulants. “This biologic phenomenon may be clinically exploitable and should be investigated further.” Also see “Psychiatry, Diagnose Thyself! Part 2” for more information on challenge studies.

MacKenzie et al. found an association between the use of stimulant medication and psychotic symptoms in children and adolescents at risk of mental illness. Psychotic symptoms were found in 62.5% of the participants who had taken stimulants versus 27.4% of participants who had not taken stimulants. All participants who had used stimulants and experienced psychotic symptoms were sons or daughters of a parent with either a major depressive disorder or bipolar disorder. “The association of current use of stimulants with current psychotic symptoms and the close temporal relationship between stimulant use and psychotic symptoms in youth who started and stopped stimulants indicated a potential causal relationship.” See “Tip of the ADHD Iceberg” for more information.

ADHD stimulants are addictive. Ritalin and Adderall are Schedule II controlled substances, meaning they are considered to have a high potential for abuse, with their use “potentially leading to severe psychological or physical dependence.” Methamphetamine adverse effects can include convulsions, memory loss, severe dental problems and even death. “Cocaine and potent stimulant pharmaceuticals, such as amphetamines and methylphenidate, produce similar effects.” The effects of amphetamines are similar to cocaine but occur slower and last longer.

Chronic abuse produces a psychosis that resembles schizophrenia and is characterized by paranoia, picking at the skin, preoccupation with one’s own thoughts, and auditory and visual hallucinations. Violent and erratic behavior is frequently seen among chronic users of amphetamines and methamphetamine.

A 2015 study by Clemow and Walker reviewed the literature on ADHD medication misuse. The authors found that elevations in brain dopamine levels seemed to be necessary to both their efficacy in ADHD and in their potential for abuse. The data suggested ADHD medication misuse was a common health care problem for stimulant medications, “with the prevalence believed to be approximately 5% to 10% of high school students and 5% to 35% of college students, depending on the study.” Conversely, nonstimulant ADHD medications did not suggest a potential for abuse. “In light of these findings, the data suggest a need for close screening and therapeutic monitoring of ADHD medication us.”

And if that is not enough to raise concerns with the use of amphetamine and methylphenidate to treat ADHD, there is evidence that challenges their long-term effectiveness. The National Institute of Mental Health (NIMH) funded a nationwide, long-term study of the effectiveness of stimulants in treating ADHD by many of the long-time advocates of stimulant medication. In 2007 the authors finally published their evaluation of long-term effectiveness. The Jensen et al. study concluded: “By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent.” The Swanson et al. study said: “All five propensity subgroups showed initial advantage of medication that disappeared by the 36-month assessment.”

So where does this leave us with regard to ADHD? Is it even a valid diagnosis? In Debunking ADHD, Michael Corrigan said ADHD diagnosis in its current form is a diagnosis of normal, using eighteen very generic, commonly observed childhood behaviors to justify giving the medications. “Coincidentally or conveniently, ordained by the all-knowing creators of ADHD as proof of ADHD’s existence, these eighteen childish behaviors … seem to drive parents and educators crazy.” ADHD is a negative label that some want you to believe is real. Like the stories of about unicorns, fairies and leprechauns, “the diagnosis of ADHD is a brilliant work of fiction.” In Our Post Human Future, Francis Fukuyama also suggested ADHD wasn’t a disease, but rather, “just the tail end of the bell curve describing the distribution of perfectly normal behavior.”

Young human beings, and particularly young boys, were not designed by evolution to sit around a desk for hours at a time paying attention to a teacher, but rather to run and play and do other physically active things. The fact that we increasingly demand that they sit still in classrooms, or that parents and teachers have less time to spend with them on interesting tasks, is what creates the impression that there is a growing disease.

For more information on ADHD, see: “ADHD: An Imbalance of Fire over Water or a Case of the Fidgets?”