Synthetic Cannabis May Pose an Even Greater Psychosis Risk

'Spice' Packs a Bigger Punch than Natural Cannabis

Deborah Brauser

December 13, 2011

December 13, 2011 (Scottsdale, Arizona) — The synthetic cannabis product known as Spice may pose a risk for psychosis in users, including those with no prior history of a psychiatric disorder, new research suggests.

A literature review, Internet sites, and even blogs spanning the past decade suggest that because it lacks the antipsychotic protective agents found in natural cannabis, Spice may pose an even greater risk of psychosis when compared with the natural product.

The results were presented here at the American Academy of Addiction Psychiatry (AAAP) 22nd Annual Meeting & Symposium.

"I would tell clinicians that when there are unexplained causes of psychosis and urine tests are coming back negative, to keep in mind that it could be caused by synthetic cannabis such as Spice," lead author Carlos Alverio, MD, a 4-year psychiatry resident from Boston University School of Medicine, Massachusetts, told Medscape Medical News.

"Also, just be aware that these substances are more potent than natural cannabis," added Dr. Alverio.

"Not for Human Consumption"

According to investigators, synthetic cannabis is often labelled as "herbal incense" and reportedly causes cannabis-like psychoactive effects. Its use led to hundreds of visits to emergency departments in 2010.

This blend of natural herbs contains the synthetic cannabinoid agonists CP-47497 and JWH-018, which have much higher binding affinities to the CB1 and CB2 cannabinoid receptors than does tetrahydrocannabinol (THC), which is found in natural cannabis. This stronger binding can lead to more potent effects.

The investigators also note that whereas natural cannabis contains cannabidiol, which is known to have antipsychotic properties, Spice does not.

Earlier this year, as reported by Medscape Medical News, the US Drug Enforcement Administration (DEA) not only temporarily banned the increasingly popular synthetic stimulants marketed as "bath salts" but also banned 5 chemicals found in synthetic cannabis products, such as Spice and K2. The banned chemicals included JWH-018 and CP-47497.

According to a news release from the DEA at the time of the ban, smokeable herbal products have become especially popular with teens and young adults because they are marketed as being legal while containing chemicals that supposedly mimic THC.

"These chemicals, however, have not been approved by the FDA for human consumption, and there is no oversight of the manufacturing process," writes the DEA.

"Young people are being harmed when they smoke these dangerous 'fake pot' products and wrongly equate the products' 'legal’ retail availability with being 'safe,' " added DEA administrator Michele M. Leonhart in the news release.

Paranoia and Hallucinations

Dr. Alverio said that it was because of the increasing number of baffling cases of psychosis being reported in emergency departments that his investigative team wanted to conduct this study.

"Clinicians found they didn't have a clear explanation for this. It seemed like a substance-induced psychotic disorder, but because the tests were coming back negative, there was a question of what was going on. So we wanted to start exploring these issues."

For the analysis, the investigators evaluated data from Medline on studies conducted from 2000 to 2011, as well as data from various Internet sources on personal experiences of using Spice.

"Articles [emphasized] chemical properties, psychotic vulnerability, and addictive properties of synthetic cannabis, and hypothetical comparisons to natural cannabis," explain the investigators.

In addition to reporting a "long-lasting high," Spice users also often reported "seeing things, hearing voices, and extreme paranoia."

Other symptoms that were reported in the 4 studies and that were found in Spice users between the ages of 20 and 40 years included anxiety, disorganization, and confusion. In addition, in 2 of these studies, those who reported psychotic symptoms also reported having no previous psychotic disorder.

The researchers note that more formal comparative studies are necessary to fully investigate the psychosis risk.

Raises Awareness

"This study was interesting because it increases awareness," Shaul Lev-Ran, MD, from the Center for Addiction and Mental Health in Toronto, Canada, told Medscape Medical News.

"We all see this in clinical work; we're seeing more and more people coming in who take Spice, and we're reading more about effects, such as myocardial infarction or agitation. But there's not enough evidence yet about what's going on," said Dr. Lev-Ran.

He added that synthetic cannabis appears to be a public health concern, but more research-based data are needed.

"The fact that we see it in the clinic is important. But we need to ground it in research. And the more of these studies that we have, the better base we'll have for our clinical judgement."

When asked if he would call the use of Spice a "trend" (such as with so-called Bath Salts), Dr. Lev-Ran answered, "not yet." He added that there is often a lag between when something is actually happening and when a trend can be seen.

"Right now I think it's still in the case report zone and not considered an epidemic. But time will tell."

Easily Available, Undetectable

Also commenting on the study, Alan J. Budny, PhD, from the Center for Addiction Research at the University of Arkansas for Medical Sciences in Little Rock, said that although "there wasn't great data" on the association between synthetic cannabis and psychosis, "it makes some sense biologically."

"So it's not clear, but it's possible. Another possibility is that because it's considered 'legal,' people who wouldn't normally do drugs might be trying this. And naive users, even of marijuana, are more at risk for the more acute side effects, such as panic symptoms," said Dr. Budny, who is also a member of the substance use disorders workgroup for the upcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Nevertheless, he noted that this is definitely a substance that clinicians should be aware of.

"Just like marijuana, it's a drug, but it's also easily available."

Dr. Budny added that some people use synthetic cannabis to "beat the tests" done to detect marijuana use. However, new, more sensitive tests are now being developed and marketed.

"Still, it's not being picked up on the regular drug tests. So it's important to be aware of this drug that's probably being passed around among peers."

The study authors, Dr. Lev-Ran, and Dr. Budny have disclosed no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 22nd Annual Meeting and Symposium: Poster Abstract 1. Presented December 9, 2011.

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