“Spiceophrenia”

Synthetic cannabimimetics and psychosis.

Not long ago, public health officials were obsessing over the possibility that “skunk” marijuana—loosely defined as marijuana exhibiting THC concentrations above 12%, and little or no cannabidiol (CBD), the second crucial ingredient in marijuana—caused psychosis. In some cases, strong pot was blamed for the onset of schizophrenia.

The evidence was never very solid for that contention, but now the same questions have arisen with respect to synthetic cannabimimetics—drugs that have THC-like effects, but no THC. They are sold as spice, incense, K2, Aroma, Krypton, Bonzai, and dozens of other product monikers, and have been called “probationer’s weed” for their ability to elude standard marijuana drug testing. Now a group of researchers drawn primarily from the University of Trieste Medical School in Italy analyzed a total of 223 relevant studies, and boiled them down to the 41 best investigations for systematic review,  to see what evidence exists for connecting spice drugs with clinical psychoses.

Average age of users was 23, and the most common compounds identified using biological specimen analysis were the now-familiar Huffman compounds, based on work at Clemson University by John W. Huffman, professor emeritus of organic chemistry: JWH-018, JWH-073, JWH-122, JWH-250. (The investigators also found CP-47,497, a cannabinoid receptor agonist developed in the 80s by Pfizer and used in scientific research.) The JWH family consists of very powerful drugs that are full agonists at CB-1 and CB-2 receptors, where, according to the study, “they are more powerful than THC itself.” What prompted the investigation was the continued arrival of users in hospitals and emergency rooms, presenting with symptoms of agitation, anxiety, panic, confusion, combativeness, paranoia, and suicidal ideation. Physical effects can includes elevated blood pressure and heart rate, nausea, hallucinations, and seizures.

One of the many problems for researchers and health officials is the lack of a widely available set of reference samples for precise identification of the welter of cannabis-like drugs now available. In addition, the synthetic cannabimimetics (SCs) are frequently mixed together, or mixed with other psychoactive compounds, making identification even more difficult. Add in the presence of masking agents, along with various herbal substances, and it becomes very difficult to find out which of the new drugs—none of which were intended for human use—are bad bets.

Availing themselves of toxicology tests, lab studies, and various surveys, the researchers, writing in Human Psychopharmacology’s Special Issue on Novel Psychoactive Substances, crunched the data related to a range of psychopathological issues reported with SCs—and the results were less than definitive. They found that many of the psychotic symptoms occurred in people who had been previously diagnosed with an existing form of mental disturbance, such as depression, ADHD, or PTSD. But they were able to determine that psychopathological syndromes were far less common with marijuana than with SCs. And those who experienced psychotic episodes on Spice-type drugs presented with “higher/more frequent levels of agitation and behavioral dyscontrol in comparison with those psychotic episodes described in marijuana misusers.”

In the end, the researchers can do no better than to conclude that “the exact risk of developing a psychosis following SC misuse cannot be calculated.” What would the researchers need to demonstrate solid causality between designer cannabis products and psychosis? More product consistency, for one thing, because “the polysubstance intake pattern typically described in SC misusers may act as a significant confounder” when it comes to developing toxicological screening tools. Perhaps most disheartening is “the large structural heterogeneity between the different SC compounds,” which limited the researchers’ ability to interpret the data.

This stuff matters, because the use of Spice-type drugs is reported to be increasing in the U.S. and Europe. Online suppliers are proliferating as well. And the drugs are particularly popular with teens and young adults. Young people are more likely to be drug-naïve or have limited exposure to strong drugs, and there is some evidence that children and adolescents are adversely affected by major exposure to drugs that interact with cannabinoid receptors in the brain. 

Graphics credit: http://scientopia.org/blogs/drugmonkey/

Strong Pot: What Do Schizophrenics Think?

Small study asks patients for their opinions.

The theory, fiercely debated in the research community, that strong cannabis can actually cause schizophrenia—or is associated with relapse in schizophrenics who smoke it—is the subject of a small study from Switzerland on outpatient schizophrenics, some of whom were pot smokers.

 A study of this kind, with only 10 subjects, verges on the anecdotal. Nonetheless, it is worth a look, just to see if any verification of the theory lurks therein.

In their paper for the open access Harm Reduction Journal—“Do patients think cannabis causes schizophrenia? A qualitative study on the causal beliefs of cannabis using patients with schizophrenia”—psychiatric workers with the Research Group on Substance Use Disorders interviewed patients who attended an outpatient clinic at the Psychiatric University Hospital in Zurich. The researchers did it because, as the paper states, “patients’ beliefs on the role of cannabis in the pathogenesis of schizophrenia have—to our knowledge—not been studied so far…”

“None of the patients described a causal link between the use of cannabis and their schizophrenia,” the researchers determined. However, several of the schizophrenics did have their own version of a disease model to account for their illness. Five of the patients attributed their schizophrenia to “upbringing under difficult circumstances,” and three placed the blame on “substances other than cannabis (e.g. hallucinogens).” The remaining two patients gave “other reasons.”

Interestingly, four of the patients “considered cannabis a therapeutic aid and reported that positive effects (reduction of anxiety and tension) prevailed over its possible disadvantages (exacerbation of positive symptoms).” The authors conclude that excluding schizophrenic patients from treatment settings because of marijuana use “may cause additional harm to this already heavily burdened patient group.”

Graphics Credit: http://www.salem-news.com

The Drug Myth That Will Not Die

Brits still pushing marijuana/schizophrenia connection.

If at first you don’t succeed....

The UK Telegraph reports that scientists at the Institute of Psychiatry in King's College London injected (yes, injected) 22 healthy men with high potency THC (not marijuana), and recorded the results. According to the leader of the study team, Dr. Paul Morrison, "These findings confirm that THC can induce a transient acute psychological reaction in psychiatrically well individuals."

The Telegraph article said the researchers found that the "extent of psychotic reaction" was not related to "the degree of anxiety or cognitive impairment" in the men.

Mary Brett, vice president of Europe Against Drugs, said: "This shows that anyone who is healthy can become psychotic by smoking cannabis. They don't already have to have a mental illness. Healthy people can become psychotic."

Well, no. Observant readers will no doubt find all of this familiar: More than a year ago, a national hysteria over “skunk” cannabis was sparked in Great Britain when the University College of London produced a study purporting to show that strong pot was literally driving people crazy. The lunacy peaked with Prime Minister Brown’s description of new strains of cannabis as 'lethal.' At the time, the London Guardian reported that "Whitehall's own panel of experts has concluded that increased marijuana use has not been matched by a corresponding rise in mental illness."

Against the advice of her own drug advisers, then-Home Secretary Jacqui Smith restored cannabis from class C to the “harder” class B status because of mental health concerns. British health authorities maintained that "skunk" cannabis was linked to the onset of schizophrenia. Since no one knows what, exactly, causes schizophrenia, and since recent findings continue to point toward genetic causes, this was a triply astonishing claim.

Colin Blakemore, a prominent professor of neuroscience at the Universities of Oxford and Warwick, tackled the issue of “pot so strong it can make you psychotic” in an article for the Guardian:

“And what of the alarming stories of horrifying powerful "skunk"? Some newspapers have told us that the level of THC, the active ingredient, in street cannabis today is 20 or 30 times higher than 10 years ago. That would be rather surprising, given that THC content was 7 per cent on average in 1995. In reality, two studies, due to be published later this year, concluded that the average THC content has doubled.”

With the latest report, King’s College has once again proven that if you inject someone with massive doses of THC, he or she will find the experience dramatically unpleasant. So do monkeys. Years ago, when researchers injected test monkeys with synthetic THC approximately one hundred times more powerful than the naturally occurring substance, the monkeys fell down and didn’t move. This was dramatic proof of... nothing in particular. But it was sensational and it made headlines.

Meanwhile, the solid fact that a minority of marijuana users experience strong withdrawal symptoms when they abstain—an important and verifiable scientific finding—remains largely unknown to the general public.


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Marijuana Panic Revisited

U.K. journal casts doubt on psychosis connection.

In May of this year, The University College of London reports that different strains of marijuana cause different types of psychological maladies. Shortly thereafter, Prime Minister Brown "publically described new strains of cannabis as 'lethal,' as if they could trigger a fatal overdose," according to an editorial in the Guardian. (See "U.K. Marijuana Panic Continues"). And in August, a mental health story run by the London Daily Mail claimed that smoking a single joint of marijuana increased the risk of developing schizophrenia by 41 per cent—an erroneous statistic that was also hotly contested by various U.K. drug experts. (See "Media Suffers Attack of Cannabis Psychosis").

Now comes a review article from the British Journal of Psychiatry, published by the Royal College of Psychiatrists, strongly suggesting that the odds of an association between cannabis and psychosis is “low.”

A group of drug experts and psychiatrists, including scientists from the University of Bristol, Imperial College London, Cambridge University, and Cardiff University undertook to “systematically review the evidence pertaining to whether cannabis affects outcome of psychotic disorders.”

The group searched relevant databases and compiled a list of more than 15,000 relevant references. A total of 13 longitudinal studies were included in the quality assessment.

The authors concluded that, despite prevailing clinical opinion, it remained “unclear” whether cannabis led to worse outcomes for people with psychosis, “or whether this impression is confounded by other factors. Specifically, the review authors noted that “few studies adjusted for baseline illness severity, and most made no adjustment for alcohol, or other potentially important confounders. Adjusting for even a few confounders often resulted in substantial attenuation of results.”

In the end, “confidence that most associations were specifically due to cannabis is low.”

Graphics Credit: COSMOS

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