New Psychoactive Substances (including kratom, synthetic cannabinoids, synthetic opioids, synthetic cathinones, and more).

Related Chapters:
Entheogens and Psychedelics

Chapter Sections:
Synthetic Opioids (e.g. Fentanyl)
Synthetic Cathinones (Mephedrone, Methylone)
Salvia Divinorum
Synthetic Cannabinoids
Others - New psychoactive substances are being developed at a rapid rate

Page last updated June 10, 2020 by Doug McVay, Editor.

61. Limited Understanding of Synthetic Cannabinoids

"Much of our understanding of cannabinoid tolerance, dependence, and withdrawal has been based on studies involving ?9-THC, a relatively weak partial agonist at CB1 and CB2 receptors. However, the SCBs [Synthetic Cannabinoids] commonly found in quasi-legal commercial products, such as K2 and Spice, are typically full cannabinoid receptor agonists. Importantly, a drug’s efficacy determines how 'powerful' its maximal effects may be in biological systems. A low efficacy cannabinoid like ?9-THC will have a less pronounced maximal effect than a higher efficacy cannabinoid, such as the SCBs present in commercial products, and this difference in maximal effects cannot be overcome simply by increasing the dose of ?9-THC. In other words, no amount of ?9-THC can stimulate cannabinoid receptors to the same degree as the SCBs currently emerging as drugs of abuse. This has left researchers working with these high efficacy SCBs in the unusual position of having to determine whether their effects are related to the unprecedented degree of cannabinoid receptor stimulation elicited by these compounds, or whether they are produced by interactions with other, noncannabinoid receptor systems."

Sherrica Tai and William E. Fantegrossi, "Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential," Current Addiction Reports, March 15, 2014, DOI 10.1007/s40429-014-0014-y.

62. "Spice" and Other Herbal Highs

"‘Spice’ and other ‘herbal’ products are often referred to as ‘legal highs’ or ‘herbal highs’, in reference to their legal status and purported natural herbal make-up (McLachlan, 2009; Lindigkeit et al., 2009; Zimmermann et al., 2009). However, albeit not controlled, it appears that most of the ingredients listed on the packaging are actually not present in the ‘Spice’ products and it is seems likely that the psychoactive effects reported are most probably due to added synthetic cannabinoids, which are not shown on the label. There is no evidence that JWH, CP and/or HU [three chemically distinct groups of synthetic cannabinoids] compounds are present in all ‘Spice’ products or even batches of the same product. Different amounts or combinations of these substances seem to have been used in different ‘Spice’ products to produce cannabis-like effects. It is possible that substances from these or other chemical groups with a cannabinoid agonist or other pharmacological activity could be added to any herbal mixture (17) (Griffiths et al., 2009).
"The emergence of new, smokable herbal products laced with synthetic cannabinoids can also be seen as a significant new development in the field of so-called ‘designer drugs’. With the appearance, for the first time, of new synthetic cannabinoids, it can be anticipated that the concept of ‘designer drugs’ being almost exclusively linked to the large series of compounds with phenethylamine and tryptamine nucleus will change significantly (18). There are more than 100 known compounds with cannabinoid receptor activity and it can be assumed that further such substances from different chemical groups will appear (with direct or indirect stimulation of CB1 receptors)."

"Understanding the 'Spice' phenomenon," European Monitoring Centre for Drugs and Drug Addiction (Luxembourg: Office for Official Publications of the European Communities, 2009), p. 21.

63. Prevalence of Synthetic Cannabinoid Use Among Young People in the US

"Synthetic marijuana, so named because it contains synthetic versions of some of the cannabinoids found in marijuana, is a recent and important addition to the smorgasbord of drugs available to young people in the US. These designer chemicals are sprayed onto herbal materials that are then sold in small packets under such brand names as Spice and K-2. They have been readily available as over-the-counter drugs on the Internet and in venues like head shops and gas stations. While many of the most widely used chemicals were scheduled by the Drug Enforcement Administration in March of 2011, making their sale no longer legal, purveyors of these products have skirted the restrictions by making small changes in the chemical composition of the cannabinoids used. Use of these products was first measured in MTF in 2011 in a tripwire question for 12th graders, asking about their frequency of use in the prior 12 months (see Table 2-2). Annual prevalence was found to be 11.4%, making synthetic marijuana the second most widely used class of illicit drug after marijuana that year. In spite of the DEA’s scheduling of the most common ingredients, use among 12th graders remained unchanged in 2012, with 11.3% annual prevalence. Eighth and 10th graders were also asked about use of these drugs in 2012, and their annual prevalence levels were 4.4% and 8.8%, respectively, making synthetic marijuana the second most widely used illicit drug among 10th graders, as well, and the third among 8th graders behind marijuana and inhalants. In 2013 use dropped appreciably in all five populations, including statistically significant drops among 12th graders, college students, and young adults. These declines continued in 2014 with significant drops in prevalence among young adults, college students, 12th and 10th graders (a decline among 8th-grade students was not statistically significant). Efforts by the DEA and various states to make their sale illegal may well have had an impact. In 2015 prevalence continued to decline for 8th, 10th, and 12th grade students, although none of the one-year declines were statistically significant. Among young adults and college students prevalence has leveled, with signs of a possible reversal in course with a slight uptick of .2 points (ns) for young adults and .6 (ns) for college students. There is a relatively low level of perceived risk for trying synthetic marijuana once or twice, despite growing evidence of serious problems resulting from the use of these drugs."

Miech, R. A., Johnston, L. D., O’Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (2016). Monitoring the Future national survey results on drug use, 1975–2015: Volume I, Secondary school students. Ann Arbor: Institute for Social Research, The University of Michigan, pp. 15-16. Available at

64. "Spice" Prohibition

"Because of health concerns and the abuse potential of herbal incense products, many have been banned in several European countries, 18 U.S. states, and the U.S. military.33,38 In March 2011, the FDA placed 5 synthetic cannabinoids (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) on Schedule I, making them illegal to possess or sell in the United States.38"

Pierre, Joseph M., "Cannabis, synthetic cannabinoids, and psychosis risk: What the evidence says," Current Psychiatry (Parsippany, NJ: September 2011) Vol. 10, No. 9, p. 56.

65. Scheduling of "Spice"

"On March 1, 2011, the DEA used its temporary scheduling authority and issued a final rule to place five synthetic cannabinoids on the list of controlled substances under Schedule I of the CSA.26 The five substances are
"• 1-pentyl-3-(1-naphthoyl)indole (JWH-018);
"• 1-butyl-3-(1-naphthoyl)indole (JWH-073);
"• 1-[2-(4-morpholinyl)ethyl]-3-(1-naphthoyl)indole (JWH-200);
"• 5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (CP-47,497); and
"• 5-(1,1-dimethyloctyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (cannabicyclohexanol; CP-47,497 C8 homologue).
"Pursuant to the temporary scheduling authority, these substances will remain on the list of Schedule I controlled substances for one year, and then may be given one six-month temporary extension. To remain on Schedule I thereafter, the substances would need to be permanently scheduled within the CSA."

Sacco, Lisa N. and Finklea, Kristin M., "Synthetic Drugs: Overview and Issues for Congress, Congressional Research Service (Washington, DC: Library of Congress, October 28, 2011), p. 6.

66. State Bans on Synthetic Cannabinoids

"At this time, forty-six (46) states and the federal government have scheduled one or more synthetic cannabinoids by statute or regulation and twenty-nine (29) states have some form of the generic language. Of the four states that have not scheduled one or more of the synthetic cannabinoids, Louisiana and Nebraska include the generic language. The only two states that have not yet scheduled any of the synthetic cannabinoids or the generic language are Maryland and Rhode Island. Maryland had four bills pending this legislative session, but was unable to get legislation passed before the session adjourned. There is still a regulation pending in Maryland that would schedule certain cannabinoids. The District of Columbia also has legislation pending. Rhode Island, however, does not have anything pending at this time."

Gray, Heather, "An Introduction to Synthetic Drugs," National Alliiance for Model State Drug Laws (Santa Fe, NM: June 2012), p. 11.

67. Schedule One and Limits on Research

"There is shared concern among researchers that adding these substances to Schedule I could hinder medical research. As previously mentioned, Professor Huffman did not intend for K2 to be consumed by humans. He is, however, against adding synthetic cannabinoids to Schedule I, asserting that there is still much to learn about synthetic cannabinoids and that placing them on Schedule I would create too many hurdles for researchers who need to access these drugs.58 Professor Huffman has created several synthetic cannabinoids that are seen as showing promise in treating skin cancers, pain, and inflammation."

Sacco, Lisa N. and Finklea, Kristin M., "Synthetic Drugs: Overview and Issues for Congress, Congressional Research Service (Washington, DC: Library of Congress, October 28, 2011), p. 13.

68. Reported Adverse Effects of Synthetic Cannabinoids

"While side effects of cannabis are well documented,7 data on human toxicity related to the use of synthetic cannabinoids remains limited. As with other NPS, products sold as synthetic cannabinoids often contain several chemicals in different concentrations, making it very difficult to determine substance-specific effects. Available knowledge on the toxicity of these compounds comes from scientific reports and clinical observations.
"Health-related problems associated with the use of synthetic cannabinoids include cardiovascular problems and psychological disorders,8 and it appears that there may be carcinogenic potential with some of the metabolites of the substances contained in these products.9
"A study published in 2011 on the severe toxicity following synthetic cannabinoid ingestion suggested that JWH-018 could lead to seizures and tachyarrhythmia (irregular heartbeat).10 In a recent review of clinical reports, addiction and withdrawal symptoms similar to those seen with cannabis abuse were also linked to the use of synthetic cannabinoids.11 An analysis of synthetic
cannabinoids in ‘spice-like’ herbal blends highlighted the increasing number of reports on suicides associated with preceding use of these products.12"

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 5.

69. Testing for Use of Synthetic Cannabinoids

"Most of the synthetic cannabinoids added as not-listed ingredients to Spice products are very difficult to detect by commonly used drug screening procedures. Apart from the analogs of THC such as HU-210, the structure of these new synthetic cannabinoids differs from that of THC, so that they probably will not trigger a positive test for cannabinoids in immunoassays of body fluids."

Fattore, Liana and Fratta, Walter "Beyond THC: the new generation of cannabinoid designer drugs," Frontiers in Behaviorial Neuroscience (Lausanne, Switzerland: September 2011) Volume 5, Article 60, p. 4.

70. Monitoring of Spice and New Psychoactive Substances

"A dramatic online snapshot of the Spice phenomenon as an emerging trend has been recently given by an important web mapping program, the Psychonaut Web Mapping Project, a European Commission-funded project involving researchers from seven European countries (Belgium, Finland, Germany, Italy, Norway, Spain, and UK), which aims to develop a web scanning system to identify newly marketed psychoactive compounds, and their combinations (e.g., ketamine and Spice, cannabis and Spice), on the basis of the information available on the Internet (Psychonaut Web Mapping Research Group, 2010). As a major result of the Project, a new and updated web-based database is now widely accessible to implement a regular monitoring of the web for novel and recreational drugs."

Fattore, Liana and Fratta, Walter "Beyond THC: the new generation of cannabinoid designer drugs," Frontiers in Behaviorial Neuroscience (Lausanne, Switzerland: September 2011) Volume 5, Article 60, p. 3.