Two new species of psychoactive mushrooms in the genus Psilocybe have been described from southern Africa, bringing the list to six known species indigenous to Africa.
This is even though Psilocybe species are amongst the most well-known and well-studied species of psychoactive mushrooms in the world, with around 140 described species.
In a paper published in the journal Mycologia this week, researchers from Stellenbosch University (SU) and citizen mycologists describe the two new species as Psilocybe ingeli and Psilocybe maluti.
Psilocybe ingeli was first found in 2023 growing in pastureland in KwaZulu-Natal by Talan Moult, a self-taught citizen mycologist. Psilocybe maluti was first found on a Free State small holding in 2021 by Daniella Mulder, who sent photos of the mushrooms for identification to Andrew Killian, one of South Africa’s leading citizen mycologists based in Somerset West.
In both instances, the unusual looking specimens were sent to Breyten van der Merwe for DNA sequencing and analysis in the lab of Prof. Karin Jacobs in SU’s Department of Microbiology. Van der Merwe, now a postgraduate student in chemical engineering at SU, is a trained mycologist and first author of the paper.
The paper also contains information on the traditional use of P. maluti by Basotho traditional healers from the mountain kingdom of Lesotho. According to the researchers, this appears to be the only recorded first-hand report of hallucinogenic mushrooms being used traditionally in Africa.
Cullen Taylor Clark, a citizen mycologist and co-author, worked with Mamosebetsi Sethathi, a Mosotho traditional healer, to document the use of P. maluti (locally known as koae-ea-lekhoaba) in traditional healing practices. This forms part of a larger effort, led by Clark, to document the use of mushrooms by indigenous groups in southern Africa.
Van der Merwe says there are very likely more southern African species in this genus, and that more citizen scientists need to become involved: “These two species were sent to me by citizen scientists. It would be impossible for a single researcher to cover a fraction of an area these mushroom enthusiasts have access to. This is the only way we will be able to further studies in African mycology.”
Jacobs echoes this sentiment: “There are only a handful of mycologists in Africa documenting local biodiversity. Considering the vast mycological diversity on the continent, it is a daunting task. Collaborating with citizen mycologists is therefore hugely beneficial. In addition to more material, collaboration also opens avenues for conversation and exploration, which can lead to documenting mycophilia (the love of mushrooms) on the African continent.”
Rehab centres in South Africa have been admitting an increasing number of codeine users in recent years. Now, the country’s medicines regulator has published a draft guideline as part of a broader effort to track suspicious codeine sales.
South Africa’s medicines regulator – the South African Health Products Regulatory Authority (SAHPRA) – has released a new draft guideline which it says will help stem the misuse of codeine. The opioid, which is found in certain pain relief medicines and cough syrups, is used by some people in large doses to get high.
Under the new draft guideline, the regulator can request sales data (and other information) from manufacturers, suppliers or distributors of any scheduled medicines. This would allow them to track the flow of codeine all the way “from the manufacturer to the dispensary, be it a clinic, pharmacy, hospital, or doctor’s practice”, SAHPRA’s communications officer, Nthabi Moloi, told Spotlight.
Why is this important? Until now, health authorities have struggled to detect suspicious sales of codeine, which is found in both prescription and over-the-counter medicines. This problem manifests in two ways. For one, recreational users can often get a continuous supply of codeine directly from pharmacies. While people are only permitted to purchase a limited amount of the drug, many bypass this simply by buying from different pharmacies. It’s largely impossible to flag these individuals since there is no centralised data on what medicines people buy across vendors (though attempts have been made to address this).
The second issue relates to wholesale supply. Following a Carte Blanche investigation flighted last year, SAHPRA confirmed that a pharmacy group was making illicit bulk sales of codeine-based cough syrups. While patients are only allowed to get codeine from a licensed health worker or pharmacist, it’s thus no surprise that it can also be found on the black market.
The new draft guideline aims to tackle both of these problems by allowing SAHPRA to request information from companies and health workers about how much codeine they’re producing, selling or dispensing and who it is being provided to. This would “enable SAHPRA to detect anomalies in the distribution of medicines prone to abuse, such as abnormally large orders by dispensaries” Moloi explains.
It is the “first phase”, she says, of the codeine care initiative – which is an effort to centralise data on all codeine sales along the entire supply chain nationally. The plan is to ensure that the regulator can flag anything from an individual who is buying large amounts of codeine from multiple vendors to a wholesaler who is selling the drug to illicit dealers.
Codeine rehab admissions triple since 2019
The draft guideline, which is now available for public comment, comes at a time in which rates of codeine addiction are soaring throughout South Africa, according to admissions data from drug and alcohol treatment facilities. Most rehabilitation centres around the country are connected to a programme called the South African Community Epidemiology Network on Drug Use (SACENDU), which collects anonymised patient data from the different centres. Professor Nadine Harker, who oversees this project says “if you look at treatment admissions over time, there has been an increase [in codeine-related admissions] over the years – steadily but definitely”.
Indeed, SACENDU’s bi-annual reports show that in the first half of 2019, 277 people who went to SACENDU-linked rehab sites said they had been misusing codeine. This amounted to 3% of all admissions. But by the first half of 2023, this percentage had tripled to 9% – totalling 749 people. (In absolute terms the number slightly less than tripled).
Even before this uptick, health workers were concerned. In the mid-2010s, a survey of 238 (mostly private sector) doctors was conducted across South Africa. It found that 85% of these practitioners were worried about the easy availability of codeine in pharmacies.
Part of the concern is driven by the fact that people who use codeine-based medicines over a long time can develop a range of health complications, including stomach ulcers and liver damage (this is particularly when the medicines contain additional substances like paracetamol). And some people are more vulnerable than others, as genetic factors play a big role in how codeine affects a person.
Why is the problem getting worse?
Part of the spike in codeine use appears to be driven by a trend among young people, who sometimes mix codeine-based cough syrups with cooldrinks. The combination is often referred to as lean, and has become a popular party drug among high school students. Research shows that codeine’s low price and general accessibility is one reason for its popularity. Harker for instance notes that it’s often available at home, where kids “can pick it up out of their mom’s medicine cabinet”.
In other cases, people appear to be relying on the drug not for recreation but to cope with psychological distress. For instance, a 2022 study for which women were interviewed at rehab centres in the Western Cape and Eastern Cape found that many had turned to pharmaceutical products to deal with everything from trauma caused by physical abuse to grief over the loss of a child.
“I just wanted the pain to go away. I wanted my mind to switch off… [the tablets] actually made me dead inside if I can say that,” one woman explained.
A lack of awareness about the dangers of codeine also seems to play a role: 94% of doctors who were surveyed agreed that patients “do not fully understand the risk of dependence in taking over-the-counter medicines containing codeine”. The lack of regulatory control may contribute to this impression: one study at South African rehab centres found that “many participants were of the view that [over-the-counter] codeine-containing medicines were not drug[s] per se due to their free availability to purchase without any real regulations or protocols guiding their sale”.
Shouldn’t we just make codeine prescription-only?
Currently, the law states that codeine-based pills can be bought over the counter only under specific conditions. For one, they have to contain another active ingredient like paracetamol or ibuprofen, and each pill can contain a maximum of 10 milligrams of codeine. A person can only buy one pack and it must contain at most 5 days’ worth of medicine (with no more than 80 milligrams a day). Anything more and a script is needed.
Liquid codeine, like cough syrups, can be bought without a script if it contains no more than 10 milligrams of codeine per teaspoon (the maximum daily dose is 80 milligrams). The bottle itself may not contain more than 100 millilitres of syrup.
Products like Gen-payne, Myprodol, and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen. (Photo: Towfiqu Barbhuiya/Unsplash)
Some researchers that spoke to Spotlight argue these restrictions are too lenient, and that codeine should be ‘up-scheduled’, meaning that it would only be available if a patient has a script, regardless of the dose or combination. By doing this, children may find it harder to get a hold of cough syrups for lean, and people may generally become more aware of the addictiveness of the drug when used over the long-term.
Indeed, there are some studies which have found this approach to be effective in other countries. Research published in the journal Addiction found that when authorities in Australia made codeine prescription-only in 2018, a large poisoning information centre in the country began to receive significantly fewer calls about codeine-related incidents (both from health workers and members of the public).
But there are also potential downsides to this strategy. For one, as Spotlight has previously reported, increased regulation may make life harder for poorer patients seeking pain relief. This is given that they would have to spend more money for a consultation and prescription if they needed codeine-based painkillers.
Andy Gray, who chairs an advisory scheduling committee at SAHPRA, details a second issue: “I’m not convinced that up-scheduling would solve the issue if what we’re dealing with [in South Africa] is illegal behaviour… If [codeine] is being smuggled out of manufacturers or wholesalers, scheduling is not going to make a difference”.
Dr Andrew Scheibe, a harm reduction researcher at the University of Pretoria, notes a third related problem that may occur. “If people do have codeine-dependence and they’re unable to access the codeine, they might likely shift to accessing opioids… on the black market”.
Scheibe highlights the United States as an example, where prescription opioids like oxycodone and fentanyl have been at the centre of a major drug epidemic. “When they tried to increase restrictions on access to those opioids then people started using heroin,” he notes. A 2022 study found that this had taken place among opioid users interviewed in Connecticut, Kentucky and Wisconsin.
Whatever the answer, researchers agree that some basic steps need to be taken to educate the public. Harker says “a lot of awareness raising needs to happen at various levels, for instance at pharmacies”. She notes that “when someone purchases codeine over the counter, it’s important for a pharmacist to engage [with them and] make the consequences known to the individual if they use it outside of the dosages indicated… And we don’t do that enough from the medical or pharmacist’s side”.
Early in the pandemic, many people who had SARS-Cov-2 infection or COVID began to report that they couldn’t shake off their symptoms even after a month or more – unusually long for a viral infection of the upper respiratory tract – or developed new, persistent symptoms soon after the infection cleared.
Although it’s still not clear what causes post-COVID conditions or “long COVID” (symptoms and conditions that develop, linger, or reoccur weeks or months after SARS-CoV-2 infection), a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons confirms the high burden of long COVID and sheds light on who’s at greatest risk.
The study, published in JAMA Network, found that people with a milder infection – including those who were vaccinated against SARS-CoV-2 and those who were infected with an Omicron variant – were more likely to recover quickly.
Recovery time was similar for subsequent infections.
“Our study underscores the important role that vaccination against COVID has played, not just in reducing the severity of an infection but also in reducing the risk of long COVID,” says Elizabeth C. Oelsner, the study’s lead author and the Herbert Irving Associate Professor of Medicine.
The study found that, between 2020 and early 2023, the median recovery time after SARS-CoV2-infection was 20 days, and more than one in five adults did not recover within three months.
Women and adults with pre-pandemic cardiovascular disease were less likely to recover within three months. Other pre-pandemic health conditions, including chronic kidney disease, diabetes, asthma, chronic lung disease, depressive symptoms, and a history of smoking, were linked to longer recovery times, but these associations were no longer significant after accounting for sex, cardiovascular disease, vaccination, and variant exposure.
“Although studies have suggested that many patients with long COVID experience mental health challenges, we did not find that depressive symptoms prior to SARS-CoV-2 infection were a major risk factor for long COVID.”
Other groups disproportionately affected by long COVID were American Indian and Alaska Native participants, in whom severe infections and longer recovery times were more common.
“Our study clearly establishes that long COVID poses a substantial personal and societal burden,” says Oelsner. “By identifying who was likely to have experienced a lengthy recovery, we have a better understanding of who should be involved in ongoing studies of how to lessen or prevent the long-term effects of SARS-CoV-2 infection.”
New research describes how a spreading wave of disruption and the flow of fluid in the brain triggers headaches, detailing the connection between the neurological symptoms associated with aura and the migraine that follows. The study, which appears in Science, also identifies new proteins that could be responsible for headaches and may serve as foundation for new migraine drugs.
“In this study, we describe the interaction between the central and peripheral nervous system brought about by increased concentrations of proteins released in the brain during an episode of spreading depolarization, a phenomenon responsible for the aura associated with migraines,” said lead author Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine. “These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies.”
It is estimated that one out of 10 people experience migraines and in about a quarter of these cases the headache is preceded by an aura, a sensory disturbance that can includes light flashes, blind spots, double vision, and tingling sensations or limb numbness. These symptoms typically appear five to 60 minutes prior to the headache.
The cause of the aura is a phenomenon called cortical spreading depression, a temporary depolarization of neurons and other cells caused by diffusion of glutamate and potassium that radiates like a wave across the brain, reducing oxygen levels and impairing blood flow. Most frequently, the depolarization event is located in the visual processing centre of the brain cortex, hence the visual symptoms that first herald a coming headache.
While migraines auras arise in the brain, the organ itself cannot sense pain. These signals must instead be transmitted from the central nervous system to the peripheral nervous system. The process of communication between the brain and peripheral sensory nerves in migraines has largely remained a mystery.
Fluid dynamics models shed light on migraine pain origins
Nedergaard and her colleagues at the University of Rochester and the University of Copenhagen are pioneers in understanding the flow of fluids in the brain. In 2012, her lab was the first to describe the glymphatic system, which uses cerebrospinal fluid (CSF) to wash away toxic proteins in the brain. In partnership with experts in fluid dynamics, the team has built detailed models of how the CSF moves in the brain and its role in transporting proteins, neurotransmitters, and other chemicals.
The most widely accepted theory is that nerve endings resting on the outer surface of the membranes that enclose the brain are responsible for the headaches that follow an aura. The new study, which was conducted in mice, describes a different route and identifies proteins, many of which are potential new drug targets, that may be responsible for activating the nerves and causing pain.
As the depolarization wave spreads, neurons release a host of inflammatory and other proteins into CSF. In a series of experiments in mice, the researchers showed how CSF transports these proteins to the trigeminal ganglion, a large bundle of nerves that rests at the base of the skull and supplies sensory information to the head and face.
It was assumed that the trigeminal ganglion, like the rest of the peripheral nervous system, rested outside the blood-brain-barrier, which tightly controls what molecules enter and leave the brain. However, the researchers identified a previously unknown gap in the barrier that allowed CSF to flow directly into the trigeminal ganglion, exposing sensory nerves to the cocktail of proteins released by the brain.
Migraine-associated proteins double during brain wave activity
Analysing the molecules, the researchers identified twelve proteins called ligands that bind with receptors on sensory nerves found in the trigeminal ganglion, potentially causing these cells to activate. The concentrations of several of these proteins found in CSF more than doubled following a cortical spreading depression. One of the proteins, calcitonin gene-related peptide (CGRP), is already the target of a new class of drugs to treat and prevent migraines called CGRP inhibitors. Other identified proteins are known to play a role in other pain conditions, such as neuropathic pain, and are likely important in migraine headaches as well.
“We have identified a new signaling pathway and several molecules that activate sensory nerves in the peripheral nervous system. Among the identified molecules are those already associated with migraines, but we didn’t know exactly how and where the migraine inducing action occurred,” said Martin Kaag Rasmussen, PhD, a postdoctoral fellow at the University of Copenhagen and first author of the study. “Defining the role of these newly identified ligand-receptor pairs may enable the discovery of new pharmacological targets, which could benefit the large portion of patients not responding to available therapies.”
The researchers also observed that the transport of proteins released in one side of the brain reaches mostly the nerves in the trigeminal ganglion on the same side, potentially explaining why pain occurs on one side of the head during most migraines.
While irritable bowel syndrome (IBS) is commonly associated with symptoms outside the intestine, it was not known whether these symptoms differed according to the subtypes of the condition. A new study published in Neurogastroenterology and Motility investigated the prevalence, and found that the IBS-M (mixed bowel habits) subtype had the highest prevalence of most extra-intestinal symptoms symptoms.
The researchers carried out a descriptive cross-sectional study patients with IBS according to Rome IV criteria. They were classified according to subtypes: IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant), and IBS-M (mixed bowel habits). Of the 4862 patients included; there were 608 IBS-D (12.5%), 1978 IBS-C (40.7%), and 2276 IBS-M (46.8%).
Participants completed a patient health questionnaire-9 (PHQ-9) score for depressive symptoms, with IBS-M the highest at 12.7 compared to 11.1 for IBS-D and 10.5 for IBS-C. They also completed an IBS-severity scoring system (IBS-SSS) questionnaire.
Overall, the study found the following results:
IBS-M:
Overweight
High IBS-SSS of 320
Depressive symptoms (80.0%)
Multiple extra-intestinal symptoms
Arthralgia (62.4%)
Chronic cervicalgia (81.0%)
Extremity numbness (64.5%)
Atopic dermatitis (28.2%)
IBS-C:
Lower body mass index
Low BS-SSS of 290
IBS-D:
Overweight (30.9%)
Higher food intolerance perception (9.5%)
History of cholecystectomy (17.8%)
Faecal incontinence (36.2%)
The authors concluded that, “The prevalence of most extra-intestinal symptoms is higher among patients with IBS-M. Further research is needed to better characterize IBS subtypes, which could potentially help refining tailored therapeutic strategies.”
