Get high with no hassles! Try our potent herbal blend! Relax with soothing bath salts! Safe and legal! Popular among individuals seeking to avoid social and legal consequences of drug use, a bewildering array of synthetic intoxicants and formerly obscure ethnobotanicals have surged to prominence in the past decade. A wider variety of intoxicants is available today than ever before, and new ones are being developed faster than scientists can identify them and legislators can outlaw them. Although they are readily available online and even in some convenience stores, media reports and poison control center statistics will attest that these “novel intoxicants” are anything but safe. For the confused clinician, here’s the lowdown on some of the products your patients are most likely to try.

Sinister Synthetics

Synthetic cannabinoids. Usually smoked or ingested, some authors refer to these products as “herbal marijuana alternatives” (Rosenbaum CD et al, J Med. Toxicol 2012;8:15–32). They may look like herbs, but this is a misnomer because the active ingredients are produced artificially and sprayed onto inert plant material. They are often sold as incense labeled “not for human consumption,” but psychedelic artwork betrays their intended use. Hundreds of synthetic cannabinoids exist, enabling manufacturers to evade detection and legislation by changing ingredients (Seely KA et al, Prog Neuropsychopharmacol Biol Psychiatry 2012 Apr 26; online ahead of print)

Synthetic cathinones. Known on the street as “bath salts,” these substances usually appear as a crystalline powder that can be smoked, snorted, or injected. Cathinones are closely related to methamphetamine and MDMA, so it’s no surprise users commonly experience euphoria, dangerously high blood pressures, and psychosis. As with synthetic cannabinoids, unscrupulous chemists make minor molecular changes to stay one step ahead of law enforcement. Bath salts are by far the most dangerous novel intoxicants currently in vogue, and many severe complications have been reported, including renal failure and severe rage (Olives TD et al, West J Emerg Med 2012;13(1):58–62).

Equivocal Ethnobotanicals

Salvia divinorum. Salvia is a Mexican herb used for centuries in religious rituals. When smoked or ingested, it induces short but intense hallucinatory experiences through activity at the kappa opioid receptor (Zawilska JB, Current Drug Abuse Reviews 2011;4:122–130). Surprisingly, salvia does not induce respiratory depression, and although media reports have associated salvia use with suicide and violence, there is little support for these claims in the medical literature. However, users may suffer severe anxiety associated with a “bad trip,” and there is at least one case report of prolonged psychosis (Rosenbaum CD et al, J Med Toxicol 2012;8(1):15–32).

Kratom. Derived from the southeast Asian tree Mitragyna speciosa, kratom is an age-old folk remedy for opiate withdrawal, pain, and other ailments (Rosenbaum CD et al, op.cit). It contains alkaloids up to 13 times more potent than morphine. Not surprisingly, high doses produce results similar to opioid intoxication. At low doses kratom has a stimulatory effect that has been compared with cocaine. Though kratom is structurally unrelated to opioids, users can experience a withdrawal syndrome similar to opioid withdrawal.

Emerging Enemies

Piperazine. Developed for treating parasitic infections, piperazine derivatives are gaining popularity as “legal ecstasy” because of their stimulant effects. Piperazine derivatives are serotonin reuptake inhibitors and receptor agonists. They are less potent than amphetamines, but their clinical effects may be indistinguishable. These substances are widely used in Great Britain and seem to be catching on in the US (Rosenbaum CD et al, J Med Toxicol 2012;8:15–32).

Methoxetamine. Known as MXE, methoxetamine is a legal analog of the dissociative anesthetic ketamine. Marketed as a “research chemical” in the United Kingdom, it is not yet popular in the United States. Little is known about this compound, but it is expected to induce euphoria, dissociation, illusions, and hallucinations in those who ingest, inhale, or inject it. Cases of sympathomimetic toxicity have been reported (Wood DM, Eur J Clin Pharmacol 2012 May;68(5):853–856).

Recognition It can be very difficult to determine when a patient’s clinical presentation is related to novel intoxicant use. The astute psychiatrist will ask patients about novel intoxicants that are common in their geographic area—a call to their local emergency room or poison control center can help identify what those are. Psychiatrists should be aware that some patients are at especially high risk of abusing novel intoxicants. These include adolescents and young adults; patients who are in the military, work in occupations with random urine testing or are on probation or parole; and patients who have signed pain contracts or have known substance use disorder. Often, unusual clinical presentations provide the best clue to novel intoxicant use. For example, I have seen previously healthy patients with negative toxicology tests present “out of the blue” with suicidal depression, mania, or delusions and hallucinations. Commonly, after the drugs wear off, their symptoms resolve much more quickly than would be expected with a primary mental illness. On the other hand, symptoms may be resistant even to prolonged treatment. In such cases a careful history—occasionally confirmed by synthetic cannabinoid testing—often reveals novel intoxicant use.

Management Since tests are unavailable and patients are not always forthcoming, psychiatrists often have to base treatment decisions on little more than suspicion. They should be vigilant about the possibility of “agitated delirium syndrome,” a condition similar to delirium tremens. Agitated delirium syndrome is potentially lethal and may require IV fluids, sedation, intubation and aggressive cooling in an emergency or intensive-care setting (Penders TM et al, Am J Drug Alcohol Abuse. 2012 Jul 11; online ahead of print).

Psychiatric hospitalization may be indicated even in non-life threatening cases. In inpatient settings, psychiatrists must be alert for withdrawal syndromes that may contribute to psychiatric symptoms or lead to medical complications. Whether inpatient or outpatient, it’s important to complete an adequate risk assessment because intoxication and withdrawal increase the risk of violence toward self or others. Once patients are stabilized, referral to structured chemical dependency treatment should be considered.

Many patients think the words “legal” and “natural” mean “safe.” This makes psychoeducation a key component of management, but political rhetoric can add extra challenges to counseling about novel intoxicant use. When fact sheets aren’t effective, metaphor can be useful. Some patients and their families “get it” when I tell them drinking drain cleaner is perfectly legal, and there’s nothing more natural than falling off a cliff.