Newly Emerging Drugs of Abuse

Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30-90 minutes, reach their maximum after 2-3 hours and last for about 4-12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.

Better understanding of the dynamics of the current U.S. overdose epidemic may aid in the development of more effective prevention and control strategies. We analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System in which accidental drug poisoning was identified as the main cause of death. By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, we provide evidence that the current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process. The 38+ year smooth exponential curve of total U.S. annual accidental drug poisoning deaths is a composite of multiple distinctive subepidemics of different drugs (primarily prescription opioids, heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with its own specific demographic and geographic characteristics.

Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests.