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Cannabinoids are any molecule that interacts with at least one of the two cannabinoid receptors in the body. CB1 And the CB2. This large class of chemicals can be divided into three parts: those produced by cannabis, called phytocannabinoids; Those that are produced inside the body, are called endogenous cannabinoids or endogenous cannabinoids; And those that are produced in a laboratory (which also do not exist in nature), are called industrial hemp. It’s this last class of new molecules, comprising both valuable research chemicals and dangerous street drugs, that we’re turning our attention to.

project Convention on Biological Diversity has covered synthetic hemp Several times in the past, including potential role in 2019 The vaping crisis. They remain of great interest among chemists, medical researchers, pharmaceutical companies, law enforcement, legal experts, public health officials, and drug users.

In the scientific literature, synthetic cannabinoids can be classified according to their primary role: as tools for learning more about cannabinoid receptors and the broader endocannabinoid system (ECS); As potential treatments for specific human health conditions; Or as a potentially dangerous recreational drug, which thrives in a world where safer, cannabis-derived cannabis is still mostly banned (even, in many cases, for research purposes). These hard-to-detect and in many cases easy-to-manufacture synthetic compounds have moved from the lab to the drug scene after being described in a research paper.

Lots of new preclinical research that project Convention on Biological Diversity Includes reports on the use of industrial hemp to elicit various aspects of ECS Operates or investigates the potential of other synthetics in the treatment of human diseases. But some recent studies focus on the third appearance of these human-made molecules as street drugs.

THC & JWH-018

The molecule is known as JWH-018 (the initials come from its creator, John W. Hoffman, who was a professor of organic chemistry at Clemson University) is a potent synthetic cannabinoid related to CB1 receptors five times larger than THC That is, roughly one-fifth of the dose produces a similar effect. JWH-018 is also likely the first synthetic cannabinoid that escaped from the lab and hit the streets in the early 2000s, best known as an ingredient in the gray market drug Spice.

despite JWH-018 has since been banned in many countries (and has been replaced by new synthetic chemicals that differ by a single seed), and is still in use in large parts of the world1 Thus, it is a topic worthy of researchers. A team from the University of Maastricht in the Netherlands recently evaluated the effects of the compound side by side THC. Their goal was to show a way to compare the neurocognitive and psychometric features of THC And the JWH-018 by equivalency not according to the measured dose but by the ‘psychotropic’ equation – in other words, subjective elevation according to subjects in previous placebo-controlled studies by the same research group.

Results of the new study published in May 2022 in the journal Frontiers in PsychiatryAnd the2 Indicates that at equivalent endogenous intoxication levels THC And the JWH-018 is actually not as different as it looks. Both impair subjects’ performance on motor tasks, divided attention, and impulse control tasks, with no significant differences between them. Both also produced what researchers considered significant psychological effects (similar to psychosis symptoms), according to subjects’ questionnaire responses. The main difference was that the dissociative effects were significantly more pronounced JWH-018 from THC.

But in the real world – due to the power JWH-018 and similar synthetic cannabinoids, and the inconsistent content of illicit smoking mixtures—the authors encourage great caution: “It is very difficult for users to anticipate maximum subjective high,” they wrote, “leading to highly unexpected neurocognitive outcomes. and common overdoses.

merapipim & spices

Mepirapim is a synthetic cannabinoid that was first mentioned in the scientific literature in 2013 after it was discovered in illegal herbal mixtures in Japan.3 The substance later appeared in a 2015 article in Japan stating that it may cause heart failure and death in combination with other medications,4 And in 2017, the authors, again based in Japan, reported a case of two people who used it recreationally along with acetylfentanyl, an analogue of fentanyl.5 One of the young men inhaled the drug and survived; The other took them intravenously and did not.

Mepirapim’s notoriety is reinforced by its association with John W. Hoffman’s famous “seasoning” ingredient: structural similarity with JWH-018, a Schedule 1 controlled substance in the United States, Mepirapim has a high potential for showing serious psychoactive and side effects.” pharmaceutical.6

However, it has been lightly studied, with few additional references in the scientific literature to date. As such, researchers have sought to further investigate the pharmacology and physiological effects of the drug, focusing on the potential for addiction. They certainly found that Mepirapim treatment “supports the maintenance of intracellular self-administration” in mice compared to a control group.

They concluded that the drug “stimulates addiction-related behaviors through neurochemical maladaptation in the brain” driven by the potent activation of the CB1 Cannabinoid receptors. But this last point is up for debate as another recent research paper dealing with Mepirapim and other new synthetic cannabinoids identified the drug as having a “minor” status. CB1 activity and these effects occur through other channels.7

More Synthetic Alphabet Soup

Two additional studies published in May 2022 seek to better understand the pharmacological activity and potential negative effects of synthetic cannabinoids consumed as recreational drugs.

The first, by Belgian and Italian researchers in the journal Drug testing and analysisAnd the8 It covers a small class of molecules expressly designed to evade legislation passed in China in July 2021 banning synthetic cannabinoids that contain one of seven generic core scaffolds. These new chemicals, called Oxide Cannabinoids, they have alternative infrastructures that make them technically legal – or at least outright illegal.

In their study, the researchers investigated the potency and efficacy (or maximum achievable effect) of both CB1 And the CB2 From five members of this new class. All five acted as complete stimuli in CB1 and partial stimuli in CB2and one in particular, called BZOchemoxizidewas extremely potent in both receptors, making it a potential abuse drug on regulators’ watch list.

The second study appears in the journal Mechanisms and methods of toxicologyAnd the9 Sharpen on a molecule called ur-144, is already widely used on its own or in combination with other illicit synthetic cannabinoids around the world. The authors based in Turkey evaluated the molecular mechanism of serious cardiovascular symptoms associated with its use.

they found it ur-144 Cell death induced by elevated levels of cytoplasmic Ca2+ (the ubiquitous intracellular calcium ion and messenger) and activation of DAPK1 (An enzyme that regulates cell death). While this may be a bit technical for the average drug user or public health official, it undoubtedly means ur-144 on the search radar. The authors call for studies to elucidate the molecular mechanisms of the drug’s cardiotoxic effects.

Nate Seltenrich, a freelance science journalist based in the San Francisco Bay Area, covers a wide range of topics including environmental health, neuroscience, and pharmacology. Copyright, Project Convention on Biological Diversity. It may not be reprinted without permission.


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