Liam Davenport

March 14, 2016

MADRID — A novel psychoactive substance, or "legal high," that has hallucinogenic effects and potentially severe adverse effects is being sold to partygoers as lysergic acid diethylamide (LSD), Spanish researchers have found.

Although the use of 25I-NBOMe, also known as "legal LSD," is currently relatively rare, it is sold under various names and in a range of forms, making it difficult for users to know what they are taking and for clinicians to develop effective treatments.

Iciar Ezquiaga, MD, a psychiatry resident at the Institut de Neuropsiquiatria i Addiccions–Parc de Salut Mar, Barcelona, Spain, who presented the data here at the European Psychiatric Association (EPA) 2016 Congress, told Medscape Medical News that she is worried by the appearance of drugs such as 25I-NBOMe, a concern exacerbated by the fact that novel compounds are appearing every year.

"When they are known and reported to the European and international conferences or groups, then another substance comes, and it gets onto the market."

Dr Iciar Ezquiaga

Moreover, she does not believe it is possible to stop the emergence of these novel drugs, because as soon as you eliminate one, another one will turns up in its place. For Dr Ezquiaga, the most worrying aspect is that there is currently no way to treat the adverse effects of 25I-NBOMe.

Rising Tide of Novel Psychoactives

Dr Ezquiaga began her presentation by saying that the use of novel psychoactive substances, which are defined as substances of abuse that are not yet illegal but may pose a public health threat, is increasing year to year.

The European Monitoring Centre for Drugs and Drug Addiction monitors more than 450 compounds. In 2014, it added 101 novel substances to its watch list, an increase of 25% over 2013.

The most commonly seen novel psychoactive substances are synthetic cannabinoids and synthetic cathinones, but Dr Ezquiaga focused on the novel phenethylamine 25I-NBOMe, or 4-iodo-2,5- dimethoxyphenyl-N-(2-methoxybenzyl) phenylamine.

This was first synthesized for research on the serotonin-2a receptor. It became popular as a recreational drug in 2011. It is sold online as legal LSD or LSD, and is ingested orally or sublingually, typically on blotting paper.

Typical doses are 0.5 to 1 mg. Peak effects, which include hallucinations and euphoria, occur after 20 minutes and last for 3 to 13 hours. Several cases of toxicity with 25I-NBOMe have been reported, along with adverse effects such as delirium, aggressive behavior, self-harm, and paranoia.

Dr Ezquiaga and colleagues investigated the prevalence and characteristics of 25I-NBOMe in Spain by using data from Energy Control, a Spanish harm-reduction nongovernmental organization whose workers go to clubs and raves (a type of large dance party), where they offer advice to drug users and also offer to analyze whatever drugs the partygoers are taking.

Between 2009 and 2015, 21,198 samples were received by Energy Control and analyzed by gas chromatography–mass spectrometry, 56 of which were 25I-NBOMe.

Hard to Keep Up

The samples of 25I-NBOMe were first detected in 2012. The number of such samples peaked at 19 in 2013. Usage then dipped but remained stable to the end of the study period, when 15 samples were detected.

In 42.8% of cases, 25I-NBOMe was bought as LSD; in 21.4% of cases, it was bought as 25I-NBOMe; in 7.1% of cases, as 25I-NBOH; in another 7.1%, as 25C-NBOMe; and in the remaining 21.4% of cases, as other substances.

The most common form of delivery was blotting paper, found in 37.5% of cases, followed by powder form in 33.9% of samples and liquid form in 10.7%. Curiously, in 5.3% of cases, the drug was sold in gummy bears (a form of candy).

Dr Ezquiaga told Medscape Medical News after her presentation that although it is "really hard to know" how representative the sample is, because it is was drawn from a small proportion of the people who take such drugs, it nevertheless offers a valuable insight.

She concluded her presentation by telling the audience that the use of novel psychoactive substances is increasing every year, but "our knowledge is not growing at the same speed as their development, which means that we still don't have any urine tests to detect novel psychoactive substances, we still don't have treatments to solve the toxicity, we don't have specific treatments, and we still have a lack of information about the pharmacology."

Dr Ezquiaga pointed out that it is "very relevant" that the Internet has become the most important marketplace for these substances, a development that represents a major shift from the manner in which illicit drugs have been bought and sold in the past.

"It's also very important to know that a lot of times, novel psychoactive substances are adulterant traditional drugs, so users should know what they are going to consume."

Potential Brain Damage

Session chair Ángela Ibáñez Cuadrado, associate professor of psychiatry at Universidad de Alcalá, Madrid, Spain, told Medscape Medical News after the session that the findings were "very interesting."

Dr Ángela Ibáñez Cuadrado

"We realize that there are a lot of drugs that we don't know about in clinical practice, so have to be aware of this," she said.

Highlighting the fact that a substantial proportion of individuals who bought 25I-NBOMe thought they were buying LSD, Dr Cuadrado continued: "This is a potential problem, because this is sold as legal LSD, and the potential implications in the future to cause damage to the brain is very important to keep in mind."

The research was supported by grants from the Instituto de Salud Carlos III and the European Commission. One coauthor is recipient of a Rio Hortega Fellowship. The other authors and Dr Cuadrado have disclosed no relevant financial relationships.

European Psychiatric Association (EPA) 2016 Congress: Presented March 13, 2016.

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