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Cannabinoid Hope for MND Potent Pot Linked to Psychosis

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Cannabinoid Hope for MND Potent Pot Linked to Psychosis Highlights from clinical trials on cannabis science RESEARCH ROUND-UP By Liam Drew SPASTICITY Cannabinoid hope for MND A clinical trial of a cannabi- noid oral spray that is used to treat people with multiple sclerosis (MS) suggests that the treatment could also ease the symptoms of motor neuron disease (MND). The treatment targets spasticity, a condition caused by the permanent contraction of muscles, which impedes a person’s movement. It is a prominent symptom of both MND and MS. In 2010, after a long history of people with MS using cannabis to self-medicate, a cannabis- based treatment to manage spasticity associated with MS was approved in the United Kingdom. Giancarlo Comi at Vita-Salute San Raffaele University in Milan, Italy, and his colleagues now suggest that this same cannabinoid preparation can ease spasticity in people with MND. decreased people’s reported psychosis — a condition in of strains containing less than In a double-blind, rand- pain levels. Future studies which a person’s perception of 10% THC. But using strains omized phase II trial, 30 people might more finely distinguish reality is distorted. that contained more than 10% received a placebo and 29 peo- the treatment’s efficacy in two The researchers surveyed THC made the probability of ple were given the cannabinoid forms of MND: amyotrophic 901 people with psychotic developing psychosis almost spray — a solution containing lateral sclerosis, in which spas- disorders, who had been five times higher than that of roughly equal amounts of tet- ticity varies in its prevalence admitted into psychiatric care non-users. rahydrocannabinol (THC) and and intensity, and the less com- at 10 sites in Europe and one Incidence of psychosis cannabidiol (CBD), the main mon primary lateral sclerosis, in Brazil, about their present varied considerably between psychoactive and non-psycho- which is often accompanied by and past cannabis consump- sites, and correlated with active components, respec- severe spasticity. tion. Their responses were both the availability of high- tively, of cannabis. Participants Lancet Neurol. 18, 155–164 then compared with those of potency cannabis and the spent two weeks finding a (2019) 1,237 people without psychiat- number of people who used dosage with which they were ric diagnoses. cannabis daily. These findings happy, and then maintained MENTAL HEALTH Consistent with previous suggest that potency contrib- that dose for four weeks. Spas- studies, psychosis was three utes considerably to regional ticity was measured before and Potent pot linked times more common in people variations in the prevalence of after treatment. to psychosis who used cannabis daily than psychosis. By looking at where Whereas spasticity wors- in people who had never used highly potent cannabis was ened slightly in the group that High-potency cannabis might the drug. The researchers most available, the research- received a placebo, it improved carry greater risks to mental then grouped the participants ers calculated that if daily in those who received the health than do less powerful according to whether they use were accepted as causing cannabinoid treatment. Of strains. An international study used strains of cannabis that psychosis, eliminating its use the participants who received led by Marta di Forti at King’s are particularly rich in THC. would reduce psychosis rates cannabinoids, 55% reported College London suggests that Compared with non-users of in London by 30% and in feeling better, compared with people who use strains that cannabis, the odds of develop- Amsterdam by 50%. only 13% of those given a contain large amounts of THC ing psychosis were more than Lancet Psychiatry 6, 427–436 placebo. The cannabinoids also are more likely to develop twice as high for daily users (2019) S20 | NATURE | VOL 572 | 29 AUGUST 2019 ©2019 Spri nger Nature Li mited. All ri ghts reserved. ©2019 Spri nger Nature Li mited. All ri ghts reserved. CANNABIS OUTLOOK PAIN IMMUNOLOGY clinical trials in several rare a firm mechanistic footing. autoimmune diseases, includ- Hepatology 69, 1535–1548 (2019) Cannabinoids’ Inflammatory ing lupus, but the compound analgesic promise inhibition might also be useful for more MENTAL HEALTH common inflammatory condi- The case of a 66-year-old A compound that targets the tions such as arthritis. CBD might bring Clin. Pharmacol. Ther. 104, woman who feels only mini- cannabinoid receptor CB2 can psychosis relief mal pain might have revealed a powerfully suppress inflamma- 675–686 (2018) new path to pain relief. Investi- tion in humans. The drug can- The psychotic effects of canna- gators think that inhibiting the didate, ajulemic acid, has no WEIGHT LOSS bis are commonly attributed to breakdown of anandamide, a psychotropic side effects, and its THC content. Conversely, fatty-acid amide that interacts strengthens the idea that CB2 Safer target for CBD seems to have anti- with cannabinoid receptors, activators offer an alternative hunger blockers psychotic properties. A small could provide long-term pain way of stopping inflammation. clinical trial indicates that relief. CB2 is almost absent from Drugs that suppress appetite CBD can relieve changes in The woman came to doc- neurons in the central nervous and promote weight loss by brain activity that are associ- tors’ attention when, following system, so activating the recep- blocking the cannabinoid ated with psychosis. an operation on her arthritic tor causes no psychotropic receptor CB1 could be back To probe CBD’s mecha- thumb, she required almost effects. It is, however, abun- on the menu, more than a nism of action, Sagnik no pain relief. Her medical dantly expressed on circulating decade after such a drug was Bhattacharyya at King’s Col- records revealed that after immune cells, and researchers withdrawn owing to its severe lege London and his colleagues a hip replacement the year have known since the 1990s psychiatric side effects. used functional magnetic before she had similarly taken that activating CB2 in rodents Rimonabant, approved in resonance imaging (fMRI) to only paracetamol. can suppress inflammation. Europe for use as an anti- see how the drug affected the James Cox at University Last year, Derek Gilroy at obesity drug in 2006 before brain activity of medication- College London, Devjit University College London and being withdrawn two years free young adults who had Srivastava at Raigmore Hos- his colleagues, in collaboration later, targets CB1 in the part of sought psychiatric help and pital in Inverness, UK, and with Corbus Pharmaceuticals the brain that controls hunger. who were considered at high their colleagues surveyed the in Norwood, Massachusetts, Blocking the receptor reduced risk of developing psychosis. woman’s genome in search showed that ajulemic acid appetite, but also interfered Participants were given of a genetic basis for her pain (developed by Corbus as with other brain functions. either a dose of CBD or a insensitivity. They discovered Lenabasum) also dampened Fresh findings suggest that placebo. The two groups were two genetic changes affecting inflammation in humans. drugs that block CB1 found then compared with healthy, an enzyme called fatty-acid only in peripheral organs such age-matched individuals as amide hydrolase (FAAH). “Altered brain as the liver could suppress they all performed a verbal FAAH degrades a number of function in people hunger without inducing learning task. Brain activity fatty-acid amides, including experiencing psychotropic side effects. was recorded using fMRI at the anandamide — an activator of psychosis could be A study in mice, led by Jie baseline and during memory the cannabinoid receptor CB1. modified by a single Liu and George Kunos at the encoding and memory recall. One of the genetic changes dose of CBD.” US National Institute on Alco- Compared with healthy was a common mutation hol Abuse and Alcoholism in people, the brains of those at that gives rise to a form of Escherichia coli bacteria Bethesda, Maryland, pinpoints high risk of psychosis showed FAAH with low activity. The killed with ultraviolet light two distinct pathways by diminished activation of the other was the deletion of a were injected into the skin of which CB1 in the liver affects striatum during encoding, short region of DNA next to healthy volunteers to generate metabolic processing. In mice and of the medial temporal the gene encoding FAAH, inflammation. Participants fed a high-fat diet, CB1 activa- lobe and midbrain during which removed a gene that were then given a placebo, a tion inhibited three inter- recall. CBD seemed to par- closely resembles FAAH. The widely used anti-inflamma- linked intracellular signalling tially reverse those changes: researchers proposed that tory steroid or ajulemic acid. components in the liver, which activation of the areas was combining these changes The researchers found that was associated with excess still depressed compared with would cause a person to both the drug candidate and glucose and insulin in the healthy individuals, but higher exhibit low FAAH activity the steroid led to a dramatic blood. Drugs that block CB1 than that in people at high risk and, therefore, a build up of decrease in the number of interfered with this pathway who were given a placebo. anandamide. The woman’s neutrophils that infiltrated and helped to normalized The study suggests that blood samples confirmed this. the injection site, as well as a glucose and insulin levels. altered brain function in people The work suggests that an decrease in the production The researchers also found experiencing psychosis could increased level of anandamide of certain pro-inflammatory that such drugs could reverse be modified by a single dose of provides long-term suppres- lipid signalling molecules. fat accumulation in the livers CBD, supporting the molecule’s sion of pain signalling, and But ajulemic acid also seemed of mice fed a high-fat diet further development as an anti- seems to clinically validate to promote clearance of the through a second pathway that psychotic compound.
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