Identifying 'Legal Highs'

By definition, a legal high is achieved by a new narcotic or psychotropic drug that is not controlled by the United Nations’ 1961 Narcotic Drugs or 1971 Psychotropic Substances Conventions. Typically, these drugs are purchased on the internet, in ‘head shops,’ at music festivals or nightclubs.

Bath Salts (Legal Highs)

Image Credit: Marcos Mesa Sam Wordley/

What substances can provide a legal high?

The substances that can provide legal highs, which are otherwise referred to as new psychoactive substances (NPS), can be sold in herbal smoking mixtures, plant materials, and extracts, tablets or powders, many of which are marketed as “plant food,” “bath salts” or “research chemicals.”

Typically, these substances are designed to mimic or replace different recreational drugs, such as cocaine, cannabis, ecstasy, 3,4-methylenedioxymethamphetamine (MDMA), and amphetamines. To date, there are 9 categories in which NPS can fall into, which include:

  • Synthetic cannabinoids/cannabimimetic
  • Cathinones/synthetic cathinones
  • MDMA-like entactogens
  • Novel stimulants
  • Synthetic opioids
  • Novel tryptamine derivatives
  • GABAergic drugs
  • Dissociatives
  • Piperazines

Synthetic cannabinoids

As the largest type of NPS, synthetic cannabinoids are typically prepared by spraying a dried plant with the synthetic cannabinoid drug. As compared to tetrahydrocannabinol (THC), which is the active ingredient in cannabis, synthetic cannabinoids often have a much greater agonistic activity at the cannabinoid CB1 receptor, thereby increasing the psychoactive effect of this type of NPS.

Researchers believe that this enhanced psychoactivity is due to the presence of an indole group in the synthetic cannabinoid, which leads to the activation of 5-HT2A receptors.

Click here to read an interview on detecting new synthetic cannabinoids.

Synthetic cathinones

Commonly marketed under the name of MCAT or meow meow, mephedrone is one of the most widely used NPS. With amphetamine-like properties, mephedrone can increase both dopamine and 5-HT levels, as well as reverse the transport of dopamine through the same mechanisms used by amphetamine.

In addition to mephedrone, other synthetic cathinones include methylone, butylone, and bupropion, the latter of which was originally developed as an antidepressant but is now used to assist smokers interested in quitting.

Regulation challenges

The international drug control system has encountered numerous challenges associated with managing the proliferation of NPS. Unfortunately, since many countries have enacted national drug laws designed to prohibit the sales of NPS, the manufacturers producing these substances often respond by continuously inventing new uncontrolled compounds that can reach the public.

To overcome these challenges, several nations including Ireland, Poland, Romania, and the United Kingdom have imposed “blanket bans.”  These bans aim to prohibit the sale of any product that is associated with psychoactive properties.

Despite the potential utility of such a law, these bans have faced intense criticism due to the challenges of enforcing such a ban, as well as the restrictions this ban could have on pharmacological research. Furthermore, the legal definition of what is “psychoactive” is vague, thereby allowing manufacturers to interpret and advertise the properties of their products in various ways.


The widespread availability of unregulated psychoactive drugs inevitably leads to a myriad of risks for the consumer. In one recent study that evaluated the legal highs offered on United Kingdom-based websites, the researchers found that retailers offered a total of 1308 items that were available in a wide variety of formulations ranging from pills and tablets to smoking blends, liquids, orodispersible strips, and chewing gum.

Of these 1308 items, only about 56% of the products were described as having clear effect claims, whereas the remainder of products had descriptions that implied specific effects that are similar to more widely known illegal drugs. In addition to a lack of information on claimed effects, this study also found that over 40% of the products did not list any ingredients and those that did claim to contain several different types of herbs or plant extracts.

Taken together, only 92% of the products identified in this study listed any side effects, and those that did had vague and poor-quality descriptions like “can make you feel a bit rough.

Overall, the lack of safety information provided by these websites, as well as many other NPS sellers, can lead to the incorrect assumption that legal highs are safe, especially among younger and/or new users. Since many of the ingredients found in NPS have not been tested for safety, there is no clear information as to what side effects these users might experience.

While this may be true, some reported symptoms associated with legal high ingestion include seizures, unconsciousness, shortness of breath, vomiting, aggression, paranoia, heart palpitations, agitation, foaming at the mouth, and even death. Given the severity of these symptoms, the lack of control over the buying and selling of NPS is a grave global public health concern.

Potential therapeutic applications

In addition to the drugs mentioned above, several older, clinically used, or clinically tested drugs have been rebranded by different websites as NPS. Some of the more common clinically used drugs that have been abused over the past decade include anesthetics, benzodiazepines, painkillers, and stimulants.

Desoxypipradrol, for example, which was previously approved for the treatment of narcolepsy several years ago, reemerged in 2009 under the name of ‘Ivory Wave.’ Similarly, a-methyltryptamine (AMT), which was previously used for the treatment of depression, has also been abused and led to numerous drug-related deaths.

Although many NPS are abused, several studies have investigated the potential utility of these drugs to treat certain clinical conditions. Several synthetic cannabinoids, for example, have been studied for their potential utility in alleviating the symptoms of Parkinson’s disease.

More specifically, these NPS have been shown to reduce L-3,4-dihydroxyphenylalanine (L-DOPA) induced dyskinesias that can occur in Parkinson’s patients. Some of the synthetic cannabinoids that have been investigated for this purpose, as well as for their potential utility in treating Alzheimer’s disease, include WIN-55,212-2 and 1,1-dimethyl heptyl-11-hydroxytetrahydrocannabinol (HU-210).

In addition to synthetic cannabinoids, certain MDMA synthetics have also been examined for their potential use in enhancing L-DOPA effects in a primate model of Parkinson’s. Since MDMA has been hypothesized to increase the efficacy of psychotherapy in treatment-resistant patients with post-traumatic stress disorder (PTSD), certain NPS with ecstasy-like activity could also be used for this purpose.

Some of the NPS that would fall into this category include 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), and 1,3-benzodioxolyl-N-methylbutanamine (MBDB).

References and Further Reading

  • Davidson, C., & Schifano, F. (2016). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry 64; 267-274. doi:10.1016/j.pnpbp.2015.07.010.
  • Norman, C., & Lee, G. A. (2017). A snapshot of novel psychoactive substances (legal highs) use in London. International Emergency Nursing 35; 56-58. doi:10.1016/j.ienj.2017.06.003.
  • Rychert, M., & Wilkins, C. (2018). A critical analysis of the implementation of a legal regulated market for new psychoactive substances (“legal highs”) in New Zealand. International Journal of Drug Policy 55; 88-94. doi:10.1016/j.drugpo.2018.02.014.
  • Schmidt, M. M., Sharma, A., Schifano, F., & Feinmann, C. (2011). “Legal highs” on the net – Evaluation of UK-based Websites, products, and product information. Forensic Science International 206(1-3); 92-97. doi:10.1016/j.forsciint.2010.06.030.

Further Reading

Last Updated: Sep 9, 2020

Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine; two nitrogen mustard alkylating agents that are used in anticancer therapy.


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