"Alongside their legitimate uses as medicines and in research, the fentanils also have a long history of illicit use as replacements for heroin and other controlled opioids. Between 1979 and 1988, more than 10 fentanils that had been made in illicit laboratories were detected on the drug market in the United States (Henderson, 1991). The first was alpha-methylfentanyl, followed by substances such as 3-methylfentanyl and 4-fluorofentanyl. Typically, they were sold as heroin or ‘synthetic heroin’.
New Psychoactive Substances (NPS)
New or novel psychoactive substances and "legal highs," including synthetic cannabinoids, mephedrone, ketamine, and more
"Reflecting consumer demand, the market in new benzodiazepines appears to have grown over the past few years. The EMCDDA is currently monitoring 23 of these substances, including six that were reported for the first time in 2016 and three during 2017. While the overall number of seizures reported by law enforcement during 2016 decreased compared with 2015, the quantity reported increased. More than half a million tablets containing new benzodiazepines such as diclazepam, etizolam, flubromazolam, flunitrazolam and fonazepam were reported during 2016 — which was about 70 % more than in 2015.
"Reflecting their use as legal replacements for cocaine, amphetamine and other controlled stimulants, there were more than 23 000 seizures of synthetic cathinones reported from across Europe in 2016 (Figure 3). These account for almost one-third of the total number of seizures of new substances over the year, and amounted to almost 1.9 tonnes, making synthetic cathinones the most commonly seized new psychoactive substances by quantity in 2016. The EMCDDA is currently monitoring 130 of these substances, including 14 that were reported for the first time in 2016 and 12 during 2017.
"Since around 2008, there has been a dramatic growth in the NPS market as globalisation and new technologies, such as the internet, have allowed them to be produced, sold and supplied on an industrial scale. Between 2009 and 2018, 119 countries and territories reported the emergence of 892 different NPS to UNODC, through the UNODC Early Warning Advisory on NPS (UNODC, 2019b). In Europe, more than 730 NPS have appeared on the drug market since monitoring began in 1997, with around 90 % of these being detected between 2008 and 2018 (EMCDDA, 2019b).
(Toxic Effects of Kratom) "During the past 3 years, there have been an increasing number of case reports15,17,29 describing unusual adverse reactions in patients who had been using kratom or kratom-based products. The acute adverse effects of kratom experienced by many users appear to be a direct result of kratom's stimulant and opioid activities.6,9,11,30,31 Stimulant effects may manifest themselves in some individuals as anxiety, irritability, and increased aggression. Opioid-like effects include sedation, nausea, constipation, and itching.
(Analgesic and opioid-like effects of Kratom) "In Southeast Asia, kratom has long been used for the management of pain and opium withdrawal.6,9-11,14 In the West, kratom is increasingly being used by individuals for the self-management of pain or withdrawal from opioid drugs such as heroin and prescription pain relievers.20,27 It is these aspects of kratom pharmacology that have received the most scientific attention.
(Current Legal Status of Kratom in the US) "Although the findings of our literature and Internet searches strongly suggest a marked increase in kratom use in the United States and Europe, kratom still appears to be somewhat of an 'underground phenomenon.' During our searches of the literature and the internet, we found no evidence that kratom is currently marketed by any of the large nutritional supplement chain stores in the United States.
(Current Use of Kratom in the US) "Evidence suggests that kratom is being used extensively for both medical and nonmedical purposes. Recent studies have shown that kratom contains a variety of active compounds that produce major pharmacologic effects at opioid and other receptors. Kratom and kratom-derived drugs may potentially be used for the management of pain, opioid withdrawal symptoms, and other clinical problems. At the same time, serious questions remain regarding the potential toxic effects and the abuse and addiction potential of kratom.
(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.