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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 86-91

New psychoactive substances: An emerging epidemic


Department of Psychiatry, Seth GSMC and KEMH, Mumbai, Maharashtra, India

Date of Submission13-Sep-2019
Date of Decision26-Oct-2019
Date of Acceptance01-Nov-2019
Date of Web Publication18-Dec-2019

Correspondence Address:
Dr. Kranti Kadam
Department of Psychiatry, Seth GSMC and KEMH, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_57_19

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  Abstract 


New psychoactive substances (NPSs) are growing at an alarming rate causing a threat to the public health. They are available online or in head shops and come with variety of street names across the cities, states, and countries. NPSs are prepared in the laboratories either by tweaking or altering the chemical structure of existing substances such as cannabis and ecstasy. They are cheap, easy to obtain, and difficult to be detected by traditional drug screening methods. It has become very challenging to detect them within the clinical settings because of the fast rate of their availability and their constant changing structure. Their purity as well as pharmacology and toxic effects are still not known. These drugs cause major life-threatening complications, which is worrisome. The legal status of these drugs is ambiguous. The laws are complex, changing, are not well defined to control or regulate their use which is a major setback. As many clinicians are unaware of the existence of such drugs, the identification and management of withdrawal syndrome and overdose become difficult. There is a need to create awareness regarding the risks and the health hazards caused by these novel substances as well as to develop and design new prevention approaches that are able to attract the attention of the young population.

Keywords: Herbal highs, new psychoactive substances, synthetic cannabinoids


How to cite this article:
Kadam K. New psychoactive substances: An emerging epidemic. Ann Indian Psychiatry 2019;3:86-91

How to cite this URL:
Kadam K. New psychoactive substances: An emerging epidemic. Ann Indian Psychiatry [serial online] 2019 [cited 2020 Jun 4];3:86-91. Available from: http://www.anip.co.in/text.asp?2019/3/2/86/273383




  Introduction Top


Human beings have been exploring various substances since ancient times. Long back, the common drugs of consumption were nicotine, alcohol, and cannabis known as gateway drugs. Then the harder drugs such as opioids and cocaine entered into the market. These drugs had just captured the young minds, but their curiosity drove them to get access to newer drugs and the drug scenario got completely changed in the last decade. These are called the new psychoactive substances (NPS). NPS have been known in the market by terms such as legal highs, herbal highs, bath salts, synthetic drugs, party pills, synthetic cocaine, herbal ecstasy, loaded, HyperDrive and NeuroBlaster, plant fertilizer, herbal incense, room deodorisers, aphrodisiac tea, social tonics, new and emerging drugs, drug analogs, and research chemicals.[1] These products can sometimes be marked as “not for human consumption.” In the last decade, India too like all the other countries has witnessed the change in the pattern of the drugs used. The factors such as easy availability, online shopping, and no regulatory control have led to the explosion of NPS into the recreational drug market. Pharmacologically, these substances affect dopamine, noradrenaline, and serotonin producing a broad spectrum of effects. A broad range of negative health outcomes have been associated with their use.[2],[3]


  What are They? Top


The United Nations Office on Drugs and Crime (UNODC) uses the term “NPS” which are defined as “substances of abuse, either in a pure form or a preparation, that are not controlled by the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, but which may pose a public health threat.”[4] These substances are created by slightly tweaking the molecular structure of existing illegal drugs such as cannabis, cocaine, and LSD.

NPS are sold in different forms such as powders, pills, smoking mixtures, liquids, capsules, plant extracts, or plant cuttings.[5] They are available in the market with variety of street names which are different across the cities, states, and the countries. They are cheap, easily available, and cannot be detected by routine screenings.

Not much is still known about their potency. Their purity as well as their pharmacology and toxic effects are largely unknown. Many of them can cause life-threatening complications. As most of the clinicians are unaware of the existence of such drugs, the identification of withdrawal symptoms and overdose becomes difficult; hence, the treatment becomes complicated.


  Who are Accessing Them More? Top


The answer is mainly adolescents and young adults. Adolescence is the tender age. The adolescents have to adapt to sudden physical as well as psychological developmental challenges. Certain factors such as peer pressure, novelty-seeking, low frustration tolerance, and high risk-taking behavior drive them to use such novel substances. It is also seen in the people who have history of illicit drug use. Another important reason is the easy availability and accessibility of such drugs. The youngsters can easily access them online. They can read the information and get attracted to them. The drugs are available online and in home shops. Their packaging is uniquely designed with flashy colors attracting the youngsters. These drugs have suddenly grown in popularity mainly because of the demand by the young population. Some studies suggest that NPS users are rather assorted and include students, prisoners, people who attend parties, injecting drug users or first-time users, and psychonauts, that is, people who experiment with psychoactive drugs, have detailed technical knowledge, and participate in online discussions sharing experiences and suggestions.[6] Few clicks are enough to supply highly psychoactive substances, cheaply and in a low-risk way, even through smartphone apps. Therefore, NPS can be sold to everyone, including very young people, in complete anonymity and easily avoiding law enforcement.


  What are Their Types? Top


The main substance groups of NPS are aminoindanes, synthetic cannabinoids, synthetic cathinones, phencyclidine-type substances (e.g. methoxetamine [MXE]), phenethylamines, piperazines, plant-based substances (e.g., kratom [Mitragyna speciosa Korth], Salvia divinorum and khat [Catha edulis]), tryptamines (e.g. alpha-methyltryptamine [AMT]), and other substances (e.g. 1,3-dimethylamylamine).

The UNODC has recently classified NPS into six categories: sedatives/hypnotics (for example, benzodiazepine-type NPS); dissociatives (for example, deschloroketamine); hallucinogens (for example, N–Methylbenzylmethoxyphenylethylamine (25I-NBOMe) derivatives; stimulants (for example, dimethylcathinone), synthetic cannabinoid receptor agonists (for example, AB-PINACA), and opioids (for example, ocfentanil) [Table 1].[2],[3]
Table 1: Provides some of the new psychoactive substances and their street names as follows

Click here to view


Phenethylamines

Phenethylamines are stimulant, entactogenic, and hallucinogenic substances that share similar chemical structures with amphetamine, catecholamines, synthetic cathinones, and other substances. Phenethylamines include both natural and synthetic substances classified into (1) classical phenethylamines such as methylenedioxymethamphetamine, methyldiethanolamine, and benzodioxolyl-N-methylbutanamine; (2) psychoactive phenethylamines that include mescaline-derived compounds such as trimethoxyamphetamine and 2,5-dimethoxy-4-methylamphetamine; and (3) more recent compounds including bromodragonfly, benzofuran, N-benzyl substituted phenethylamines substances, and the “2C-series” (e.g., 2C-I, 2C-E, and 2C-B).[7]

Piperazines

These are products of synthesis originally marketed as antihelminthic substances and proposed later as antidepressant drugs.[8] They include benzylpiperazines (BZP, 1-methyl-4-benzylpiperazine, and dibenzylpiperazine and phenylpiperazines ([3-trifluoromethylphenylpiperazine], 1-[3-chlorophenyl] piperazine, 1-methyl-3-phenylpiperazine, and para-methoxyphenylpiperazine). They are claimed by suppliers to be herbal products, but piperazine and its derivatives are all synthetic substances. BZPs have a chemical structure similar to amphetamine, but only one-tenth of its potency and are likely involved in both dopamine and noradrenaline release and inhibition of monoamine reuptake.[9] Piperazines can be found in pills or powder. Effects induced by piperazines are similar to amphetamine, but with lower intensity.[8]


  Ketamine and Phencyclidine-Type substances/dissociatives Top


This class of NPS includes substances that cause primarily dissociative effects and have chemical structure similar to phencyclidine and ketamine, for example, MXE, diphenidine, methoxphenidine, and dextromethorphan.[10] MXE is marketed as “safer” alternative to ketamine with different street names, such as “Special K,” “Mexxy,” “M-ket,” “MEX,” “Kmax,” “Special M,” “MA,” “legal ketamine,” “Jipper,” and “Roflcoptr.”[11] Ketamine an anesthetic which acts as a stimulant at low doses and a hallucinogen at high doses. Popularly known as “kit kat” and “super k” is often sold as ecstasy. It is one of the most widespread NPS in Asia. MXE is found as white powder, tablets, capsules, or as liquid, alone or in combination with other drugs, and is used by ingestion, sublingual consumption, nasal insufflations (sniffing or snorting), intramuscular or intravenous injections, or rectal administration.


  Tryptamines Top


Tryptamines are natural compounds or designer drugs that originate from the decarboxylation of tryptophan. Synthetic tryptamines are derived from modifications of natural tryptamines. LSD, for example, is obtained by the modification of lysergic acid amine, an analog present in the seeds of Argyreia nervosa and Ipomoea violacea.[12] Recently, abused novel tryptamines are AMT, 5-methoxy-AMT (5-MeO-AMT), 5-MeO-N, and N-diisopropyltryptamine, known with the streets name of “foxy” or “foxy methoxy.” Tryptamines are sold as tablets or powder and consumed through different routes of administration.


  Gaba Receptor Agonists Top


Gamma-hydroxybutyric acid (GHB) is a fatty acid present in the human brain, synthesized in 1874 and approved by the FDA in 2002 for treatment of narcolepsy.[13] It acts mainly as GABAB receptor agonist, but it also increases dopamine levels by inhibiting reuptake. GHB started being abused in bodybuilding gyms (to stimulate release of the endogenous growth hormone) and during parties for its desired effects that include increased euphoria and sexual arousal. GHB possesses rewarding properties and may induce dependence.[14] Phenazepam is a benzodiazepine synthesized in Russia in 1975 and used for treating anxiety, convulsions, and alcohol withdrawal that started being abused in 1999. It is a full GABAA receptor agonist that can lead to death if used in combination with other substances.[15]


  Synthetic Cannabinoids Top


Unlike Δ9-tetrahydrocannabinol (THC), synthetic cannabinoids are extremely potent, highly efficacious, and full agonists of the cannabinoid receptors,[16],[17] including CB1 receptors in the brain.[18],[19],[20],[21],[22],[23] They are often laced onto herbal products and sold as spice, K2, etc., Cannabis use has potential for inducing psychosis. Due to their high potency, even short or occasional use of these synthetic compounds can produce unwanted effects, such as insomnia, memory impairment, headaches, dizziness, and delusions. Cannabidiol antagonizes the psychotomimetic and other psychotropic effects of THC, although the mechanisms underlying its therapeutic effect are still not clear.[24] Compared with natural cannabis, synthetic cannabinoids may cause more frequent and more severe unwanted negative effects and may have high-risk for psychosis, especially in young users.[25]


  Synthetic Cathinones Top


Commonly known as “bath salts,” these are the analogs/derivatives of the internationally controlled substance cathinone, one of the active components of the khat plant. Similar to the action of other psychostimulants, synthetic cathinones have an effect on plasma membrane transporters of the monoamine neurotransmitters, dopamine, norepinephrine, and serotonin. Mephedrone and methylone, but not methylenedioxypyrovalerone, act as nonselective transporter agonists, thereby promoting the release of all of these neurotransmitters. Synthetic cathinones are marketed as cheap substitutes for other stimulants such as methamphetamine and cocaine.[26] People typically swallow, snort, smoke, or inject synthetic cathinones. Much is still unknown about how the chemicals in synthetic cathinones affect the human brain. Synthetic cathinones can cause paranoia, increased sociability, increased sex drive, hallucinations, and panic attacks. Intoxication from synthetic cathinones has led to death.[27]

Synthetic opioids

The opioid epidemic in the United States is thought to have led to the widespread emergence of opioid misuse across Europe.[28] It has also been suggested that heroin shortages in Europe in 2015 drove this phenomenon. In addition to fentanyls, other novel synthetic opioids with chemical structures different from fentanyl, i.e., MT-45, AH-7921, and U-47700, have appeared on the recreational drug market and are causing intoxication and potentially fatal outcomes in consumers. MT-45 (1-cyclohexyl-4- [1,2-diphenylethyl [piperazine]), has shown particular effects, such as paresthesia in limbs, hand weakness, balance disturbances, vision impairments, and hearing impairment or loss.[29] Novel opioids account for 4% of newly emerging substances but are associated with greater harm than any other NPS category. The most common form of fentanyl is powder, but they have also been detected in liquids and tablets. Due to the narrow therapeutic index of fentanyl (and, presumably, of its analogs), its recreational use is highly dangerous, especially in opioid-intolerant users. High doses might hasten death due to respiratory arrest and pulmonary edema.

Plant-based substances

This group includes Kratom (M. speciosa Korth), a plant indigenous to Southeast Asia that contains the alkaloid mitragynine; a stimulant at low doses and sedative at high doses. S. divinorum, a plant indigenous to forest areas in Oxaca, Mexico, contains the active ingredient salvinorin A which is a hallucinogenic substance. Khat (C. edulis) is a plant native of Africa and the Arabian peninsula, whose leaves are chewed, resulting in the release of the stimulants cathinone and cathine.[2]


  Health Hazards Top


At the rate they are produced, it is impossible to predict the complications that users should expect. They are unregulated and untested, and the same product may have different constituents from patch to patch due to which the users are prone to developing overdose which could be fatal. The health hazards scan is physical or psychological, including cardiovascular problems, seizures, renal failure, myocardial infarction, anxiety, agitation, memory loss, depression, psychosis, and suicide. They have also been implicated, through intravenous injections and sharing needles, thus are at risk of developing life-threatening complications such as hepatitis B, hepatitis C, and HIV/AIDS. The complications can be developed if there is concomitant use of alcohol or the other drugs along with NPS. In general, side effects of NPS range from seizures to agitation, aggression, acute psychosis, as well as potential development of dependence. NPS users have frequently been hospitalized with severe intoxications. Safety data on toxicity and carcinogenic potential of many NPS are not available or very limited, and information on long-term adverse effects or risks are still largely unknown. Purity and composition of products containing NPS are often not known, which places users at high risk as evidenced by hospital emergency admissions and deaths, sometimes associated with polysubstance use.

Laboratory challenges

Most of the clinicians are unaware of the existence of NPS. When patients present with acute withdrawal syndrome or complications like overdose, the clinicians are not able to identify them and hence the treatment becomes difficult. Some hospital settings do not have the sophisticated analytical technology available for identifying NPS, especially when new drugs first appear on the market. The structure of NPS keeps on changing so fast that these substances cannot be detected in urine with routine screening methods. Toxicology laboratories play a crucial role in the assessment of identifying acute harms that might be associated with NPS use. Having the centralized laboratories capable of keeping the testing protocols updated will ensure successful detection of NPS.


  Regulation and Legislation Top


The legal status of these drugs is quite ambiguous. The laws are complex, changing, are not well defined to control or regulate their use, which is a major setback. The alarming rate at which the NPS with their altered structures are growing, the governments of several countries have recognized the need for new mechanisms of control with accelerated ways to curtail the free sale and distribution of these substances.[30] In Europe, since 1997, three levels of control were introduced: Early Warning System, risk assessments of newly emerged substances performed by the European Monitoring Centre for Drugs and Drug Addiction scientific committee, and European Council decisions advocating new legislations.[31],[32] Some countries such as Denmark, the UK, and Israel opted for “temporary bans” of NPS considered to pose danger to public health during which a risk assessment of a particular compound could be performed, thus facilitating its subsequent inclusion into the Dangerous Drugs Ordinance.[33] Other countries such as New Zealand, Ireland, Poland, and Romania chose “premarket approval” regulation regime for synthetic drugs that pose low health risk on the base of preclinical and clinical evidence.[34] The effectiveness of these legal measures and regulations on the selling and marketing of the NPS has still to be assessed. NPS are usually produced in clandestine laboratories or diverted by licensed manufacturers. The lack of control and data on these substances make it challenging for law enforcement to clamp down on the manufacture, trafficking, and distribution of NPS.


  Indian Scene Top


NPSs are not novel to Indian market, although the data are limited. There are continuous media reports about the seizure as well as the use of a particular NPS, Meow Meow (mephedrone) in many metropolitan cities in India.[35] Mephedrone has gained tremendous popularity among Indian teenagers recently. It is a lot cheaper than cocaine, selling for Rs. 150/g versus Rs. 3000/g for cocaine. Mephedrone, manufactured in India and China, is marketed as plant feed or bath salts on the internet.[36] According to one report, almost 8 out of 10 drug users in Mumbai city are using this cheap party drug.[37] Initially, the drug was not in the list of banned drugs in India but was included in the list in March 2015. The first nationwide survey indicated new emerging trend of substance use in India with amphetamine-like substances (ATS) are being more used in specific regions like Goa and Ahmedabad.[38] These drugs have caught the fancy of the new affluent young generation of India.[39] The rave parties at Goa begun in mid-seventies known as Hippi culture. In recent years, Ecstasy had been tried extensively in clubs at Goa, and there are also structured or unstructured channels for ketamine, according to Goa police. One of the local widely available pills called CK1 pills now trending in clubs as party drugs at Goa. The pill combines cocaine and ketamine. It is sold by its street names Blizzard and Calvin Klein.[40] In the North, Kullu valley is known for its full-moon jungle rave parties. In the South, Bangalore has also turned into a rave hotspot.[41] There is lack of awareness about the pharmacology and toxic effects of these drugs among the health professionals in India.

Future recommendations

There is a need to understand the potential health and social impact of these substances and also to identify appropriate demand reduction strategies. These strategies can be implemented by imparting education on NPS among schools and colleges. The drug treatment information and emergency help can be provided through helpline services. Internet-based harm reduction and prevention programs can be devised and implemented.


  Conclusion Top


NPS pose a serious public health crisis. There is sudden explosive emergence of these substances which has caused an epidemic of toxic exposures. Unfortunately, this area is still poorly investigated, and very limited information is available so far of their nature and potential risks. The health professionals should maintain a high degree of alertness for NPS use and their possible psychological effects among vulnerable people. The phenomenon of NPS requires multidisciplinary research in areas of epidemiology, pharmacology, and prevention. Research-guided prevention education would help us overcome this global health problem. The societal and political sensitization on this issue is the need of the hour.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Introduction
What are They?
Who are Accessin...
What are Their T...
Ketamine and Phe...
Tryptamines
Gaba Receptor Ag...
Synthetic Cannab...
Synthetic Cathinones
Health Hazards
Regulation and L...
Indian Scene
Conclusion
References
Article Tables

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