Interest in the use of medical marijuana, or more specifically THC, has grown significantly in recent years, with research suggesting it could be used to relieve pain, treat muscle spasms in multiple sclerosis, stimulate appetite in cancer patients and even shrink some tumors, to name a few. But then there are the drawbacks: memory problems, anxiety and dependence, which all reduce its desirability as a therapeutic agent.
Encouragingly, scientists have now begun to reveal the mechanisms behind these dual effects, successfully teasing apart the good ones from the bad in the lab. This raises the possibility that in the future, researchers may be able to create synthetic versions of the drug that come without many of the negatives. The study has been published in PLOS Biology.
THC, the main psychoactive ingredient in marijuana, acts on the body by sticking to receptors of the so-called endocannabinoid system. This collection of molecules and receptors is involved in the regulation of various physiological processes and pathways, including pain perception and appetite. This knowledge has led to its recognition as a potential therapeutic agent, but unfortunately its use has been limited because scientists didn’t understand the mechanisms that dissociate its various positive and negative effects.
To see if they could shed light on this grey area, researchers from the University of East Anglia and the University Pompeu Fabra began conducting behavioral studies on rodents that they exposed to THC, such as exposing their paws to hot plates and examining their reactions. Using mice designed to lack one of the serotonin receptors, they found that the pain-relieving and amnesic effects of THC are independent of each other. So while these mutant mice didn’t lose their memories on THC, the drug still acted as a pain-reliever in them.
Interestingly, prior research has demonstrated that the serotonin receptor in question and one of the receptors THC binds to are found together in a brain region called the hippocampus, where they assist in memory processing. They are also coexpressed in various other areas that are known to be involved in reward processing and anxiety, leading the researchers to believe that some kind of previously unidentified interaction between them could be occurring and underlying the observed effects.
To test this out, they made cells in a dish produce both receptors, and in agreement with their idea, they found that they came together to form complexes. Importantly, they found that these complexes are also present and active in areas of the brain involved in memory impairment. Armed with this knowledge, the researchers designed synthetic compounds that prevent the receptors from coming together in mice. Remarkably, these eliminated the memory impairments elicited by THC, but did not reduce its other beneficial effects, such as the ability to relieve pain.
“This research is important because it identifies a way to reduce some of what, in medical treatment, are usually thought of as THC’s unwanted side effects, while maintaining several important benefits including pain reduction,” study author Dr. Peter McCormick said in a statement.
“Patients should not use cannabis to self-medicate, but I hope that our research will lead to a safe synthetic equivalent being available in the future.”
