New findings on how CBD and THC – the psychoactive compound in cannabis – affect the brain when administered together, could help to develop new cannabinoid therapeutics, scientists say.
A study has investigated the impact on the brain of CBD and THC, both as separate entities and when co-administered.
Researchers at University College London (UCL) analysed data from previous studies, including one which used functional Magnetic Resonance Imaging (fMRI) technology to measure brain activity in participants taking CBD and THC.
For the first time, they explored the response of the striatum region of the brain – a major part of the motor and reward systems. This is a critical component of numerous aspects of cognition, including motor and action planning, decision-making and motivation.
One study compared inhaled cannabis containing 8 mg THC, 8 mg THC + 10 mg CBD and a placebo. It showed strong disruptive effects of both THC and THC + CBD on connectivity in the associative and sensorimotor networks.
However it also identified a “specific effect of THC” in the limbic striatum network which was not present in the THC + CBD condition.
In a second study, testing oral 600 mg CBD versus placebo, CBD increased connectivity in the associative network, but produced only relatively minor disruptions in the limbic and sensorimotor networks.
The study concludes that THC “strongly disrupts striato-cortical networks” but that this effect is mitigated by the co-administration of CBD.
It states: “Oral CBD administered has a more complex effect profile of relative increases and decreases in connectivity.
“The insula [part of the brain implemented in diverse functions including emotions and self-awareness] emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis-related disorders, and the development of cannabinoid therapeutics.”
This is the first report in human subjects of data from THC, THC + CBD and CBD use achieved “using a unified set of analysis methods, and with all comparisons performed in a placebo-controlled, double-blind design”.
Read the full report here.
Researchers are using firefly genes to understand cannabis biology
Scientists know very little about how cannabinoid biosynthesis is controlled.
Scientists at the University of Connecticut are using the light-producing genes in fireflies to understand cannabis biology. The researchers hope the study will aid hemp farmers with the common problem of overproducing THC.
Cannabinoids are produced by trichomes, small spikey protrusions on the surface of cannabis flowers. Beyond this fact, scientists know very little about how cannabinoid biosynthesis is controlled.
Researchers at the University of Connecticut (UConn) are using funding from the US Department of Agriculture to discover the underlying molecular mechanisms behind trichrome development and cannabinoid synthesis. To do this, they will be looking at firefly genes.
The project is led by UConn research assistant professor Yi Ma and Gerry Berkowitz, professor in the College of Agriculture, Health and Natural Resources.
Berkowitz and Ma discovered factors responsible for trichome initiation and cannabinoid biosynthesis. In this case, the factors cause epidermal cells on the flowers to morph into trichomes. The team’s discovery was recently published as a feature article in Plants. Related trichome research was also published in Plant Direct. Due to the gene’s potential economic impact, UConn has filed a provisional patent application on the technology.
With this new grant, the researchers will continue to explore how these factors play a role in trichome development during flower maturation. To do this, the researchers are making copies of firefly luciferase, the gene that allows fireflies to light up. The luciferase gene will be fused to the cannabis plant to generate light, indicating when there is an increase in trichome development.
“It’s a nifty way to evaluate signals that orchestrate cannabinoid synthesis and trichome development,” says Berkowitz.
Ma and Berkowitz will use an instrument called a luminometer, which measures how much light comes from the sample. This will tell the researchers if the regions they are looking at are controlled by the factors responsible for increasing trichome development.
Most cannabis farmers grow hemp, a variety of cannabis with naturally lower THC levels than cannabis. Currently, most hemp varieties that have high CBD levels also contain THC, sometimes at higher levels than is allowed.
This is likely because the hemp plants still make the enzyme that produces THC. In countries and regions where THC is illegal, hemp farmers must ensure the plant contains less than a certain percentage of THC. If it exceeds the limit, in many cases it must be destroyed. A better understanding of how the plant produces THC means scientists could selectively knock out the enzyme that synthesises THC using genome editing techniques. This would produce plants with lower levels of or no THC.
“We envision that the fundamental knowledge obtained can be translated into novel genetic tools and strategies to improve the cannabinoid profile, aid hemp farmers with the common problem of overproducing THC, and benefit human health,” the researchers say.
On the other hand, this knowledge could lead to the production of cannabis plants that produce more of a desired cannabinoid, which could prove helpful in altering the content of medical cannabis products.
In addition to sharing these findings with cannabis scientists, industry and growers, the researchers will incorporate this new knowledge into UConn courses on cannabis horticulture. The grant will also support the training of undergraduates interested in cannabis research, providing them with the skills to enter the workforce.
Jazz Pharmaceuticals announes top-line results from Phase 3 trial on MS
Nabiximols oromucosal spray continues to be evaluated in ongoing clinical trials in multiple sclerosis spasticity.
The safety profile in a recent phase 3 trial on multiple sclerosis was consistent with previously reported adverse events, with no new safety signals attributable to nabiximols oromucosal spray.
Jazz Pharmaceuticals announced top-line results from its Phase 3 ‘RELEASE MSS1’ trial today (28 June), evaluating nabiximols oromucosal spray on clinical measures of spasticity in individuals with multiple sclerosis (MS).
Nabiximols oromucosal spray (branded as Sativex) is a complex botanical mixture formulated from extracts of the cannabis sativa plant and contains the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as other cannabinoid and non-cannabinoid components.
Nabiximols spray was first approved in the UK in 2010 and has been approved in 29 countries for the treatment of adult patients with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity medication.
“We remain committed to the nabiximols program and are actively assessing the RELEASE MSS1 trial results, which will be presented at a future medical meeting. We look forward to additional data from two other ongoing trials that have the potential to support a US FDA New Drug Application submission,” said Rob Iannone, global head of research and development at Jazz Pharmaceuticals.
“I would like to extend a heartfelt thank you to all those who supported and made this study possible, including the patients who were enrolled, their families, our investigators, staff, and all of the dedicated Jazz employees.”
RELEASE MSS1 was the first, and smallest, of the three clinical trials in the current program. It evaluated the safety and efficacy of nabiximols spray in 68 patients with MS spasticity. Data from these trials will continue to be evaluated as it becomes available to support the overall registrational program in the US
Two additional, ongoing Phase 3 trials are underway which will inform a comprehensive development plan.
RELEASE MSS3 is a Phase 3 multicenter, double-blind, placebo-controlled trial evaluating the efficacy of nabiximols oromucosal spray for the improvement of muscle spasms associated with MS over a 12-week treatment period. The estimated enrollment is 446 participants.
Jazz Pharmaceuticals will also run a randomised double-blind trial called RELEASE MSS5. The Phase 3 multicenter, placebo-controlled crossover trial will evaluate the effect of multiple doses of nabiximols spray on a clinical measure of velocity-dependent muscle tone in the lower limbs (Lower Limb Muscle Tone-6). 190 participants are expected to be enrolled on the trial.
Full data from the RELEASE MSS1 trial will be submitted for presentation at a future medical meeting, the company said.
UK doctors present “leading” research on medical cannabis
Doctors from Sapphire Clinics will present 20 pieces of research to the International Cannabinoid Research Society.
Doctors from Sapphire Medical Clinic will present major findings on medical cannabis at an international conference this weekend.
Since 2018 doctors in the UK have been prescribing medical cannabis for several conditions, such as chronic pain, anxiety, and post-traumatic stress disorder.
Whilst an increasing number of patients are now receiving therapy, a critical barrier to access is a lack of the right evidence to enable the NHS to fund medical cannabis.
However, thanks to the efforts of doctors and scientists the UK is now leading the way in medical cannabis research.
On Saturday 25 June, doctors from Sapphire Medical Clinics will present 20 individual pieces of research at the annual International Cannabinoid Research Society (ICRS) Annual Conference in Galway, Ireland.
In this they will describe the outcomes and safety of medical cannabis therapy in patients with a wide spectrum of disorders, including, but not limited to, chronic pain, anxiety, post-traumatic stress disorder, insomnia, and childhood epilepsy.
Within this plethora of research, they will present data from the largest bespoke medical cannabis registry in Europe, the UK Medical Cannabis Registry, which has now enrolled over 5,000 patients.
This latest analysis reports the outcomes of nearly 2,833 patients with a range of conditions for which medical cannabis was prescribed since 2019.
The conditions included chronic non-cancer pain, anxiety, fibromyalgia, and neuropathic pain. The average age of the patients was 42 years and 43 per cent were women. The patients were assessed across a variety of validated metrics to assess changes in health at one, three, six and 12 months.
The researchers report: “This study, the largest observational series of patients prescribed cannabis-based medicinal products in the UK, demonstrates an association with improved general health-related quality of life up to 12 months.
In addition, specific improvements in generalised anxiety and sleep quality were also observed. The majority of adverse events were mild and moderate.”
They added: “Whilst randomised controlled trials are essential to determine causality, this study helps inform current clinical practice and future trials, whilst also being a fundamental component of pharmacovigilance.”
Apart from pain, the researchers presented other studies looking at medical cannabis for the treatment of palliative care, headache disorders, insomnia, depression, post-traumatic stress disorder and inflammatory bowel disease.
Commenting on the findings, Dr Simon Erridge, head of research and access at Sapphire Medical Clinics, said: “Medical cannabis is not a panacea, and not all patients respond to therapy.
“However, we do know from the latest review of the literature published in the British Medical Journal of medical cannabis oils in chronic pain that they produce, on average, a 10 per cent improvement in pain scores in patients. That may not sound a lot – but for patients where nothing else has helped, this reduction in pain is greatly valued.”
He added: “The research we are presenting at ICRS is very complementary to existing studies and helps us to further understand the long-term effects of therapy. Most notably we have demonstrated both condition-specific and overall improvements to health-related quality of life. These outcomes are reported by patients and directly reflect changes they experience in day-to-day life.”
The research also showed that alongside patients who were new to cannabis, those who had previously been accessing it illicitly also reported improvements.
Dr Erridge continued: “Another very interesting finding that we have demonstrated through sub-group analysis is that in addition to patients who were naïve to cannabis having an overall improvement as a group, a similar effect size was also seen in those previously accessing illicit cannabis. This suggests that the quality and consistency of medical cannabis prescribed by a trained professional is an important facet of cannabis-based therapy.”
He described the UK as a “leader” in medical cannabis research, but went onto highlight the need for national bodies to fund more randomised control trials alongside real-world evidence.
He added: “We are pleased that through collecting, analysing, and publishing this data we are playing our part in ensuring the UK is a leader in medical cannabis research. However, randomised controlled trials are still necessary.
“For the UK to remain on the front foot it is important that funding bodies, such as the National Institute for Health Research, recognise the promising signals we present in our research and the potential impact these may have through committing funding towards further randomised controlled trials.”
“In the meantime, we will continue to publish the promising real-world effects seen in UK patients.”
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