During the last week of November, the XXIV Annual Meeting of the Sociedad Española de Investigación sobre Cannabinoides (Spanish Society for Research on Cannabinoids – SEIC) was held in Cordoba. The venue chosen for the occasion was the Auditorium of the Cordoba Visitors Centre. As in previous years, most of the participants were young researchers, who presented their results during the conference. These showed that the scientific quality of research in the field of cannabinoids by Spanish groups remains at a very high level.
The meeting was opened after a few words from the President of the SEIC, Cristina Sánchez, and the head of the SEIC Organising Committee, Verónica Sánchez, who welcomed all the attendees and highlighted the importance of holding this national conference in Cordoba, especially in the year in which the Ministry of Health has put into practice the Royal decree for the regulation of medical cannabis. This context provides a key opportunity to analyse, from a scientific perspective, the therapeutic use of cannabinoid compounds in the medical field.
The scientific part of the conference began with the inaugural talk given by Prof. Dr. Manuel Guzmán, Professor of the Department of Biochemistry and Molecular Biology at the Universidad Complutense of Madrid. Manuel is an internationally recognised researcher in the field of cannabinoids, to whom the International Cannabinoid Research Society (ICRS) awarded the prestigious Mechoulam Award 2024. In his lecture, Manuel discussed the anti-tumour effect of cannabinoids and gave a historical overview of the progress made in this field, highlighting the pioneering role of his research team in the development of these studies. Manuel shared details of their early research, in which they analysed the molecular mechanisms responsible for the anti-tumour activity of cannabinoids and the factors that generate resistance to treatment in some cancer cells. He also discussed clinical trials in glioblastoma patients to assess the anti-tumour potential of these compounds. His laboratory actively participated in the first pilot trial conducted in Spain with 9 patients, which prompted the British company GW Pharmaceuticals to conduct a randomised, double-blind, placebo-controlled phase 1b trial. Subsequently, a third phase 2 trial was conducted in Australia, which, while showing no benefit against tumour progression, showed that standardised cannabis oils improved patients' quality of life. Based on these trials, two additional studies have been launched. Manuel concluded his lecture by pointing out that there is strong preclinical evidence to support the antitumour effect of cannabinoids and that clinical trials in recurrent glioblastoma seem to confirm this.
After the lunch break, the meeting resumed with the first of the scheduled sessions. During this session, several papers were presented that provided new insights into the endocannabinoid system and its role in physiological and pathological processes. A relevant finding was that some astrocytes possess the ability to produce and release in a calcium-dependent manner the endocannabinoid 2-arachidonoylglycerol in response to specific stimuli, similar to the mechanism observed in neurons. Furthermore, advances in research on interactions between proteins and cannabinoid receptor type 1 (CB1) were discussed, with the identification of the gamma isoform of protein kinase C as a key interactor regulating the expression, signalling and function of receptor CB1. It was also pointed out that blocking CB1 receptors located in the periphery of the nervous system can improve cognitive performance in mice in a sex-dependent manner; finally, the importance of future research to elucidate the molecular mechanisms underlying interactions between CB1 receptors and NMDARs to evaluate new therapies for AD patients was highlighted. The second session of oral presentations delved into the pathophysiology of the nervous system, with a particular focus on the involvement of the endocannabinoid system in neuropsychiatric and developmental disorders. It was highlighted that blocking CB1 receptors can mitigate some of the symptoms associated with SATB2 syndrome and Fragile X syndrome. In addition, results were shared showing the link between the endocannabinoid system and schizophrenia, through the analysis of endocannabinoids and lipids in cultures of cells taken from patients' olfactory neuroepithelium.
On the second day of the congress, sessions dedicated to behaviour and addiction addressed key issues related to the endocannabinoid system and its implications for the regulation of mostly addictive behaviours. It was highlighted that CB1 receptors in the retina play a crucial role in the detection of impending visual threats and the activation of defensive responses, while their absence in neurons with D1R dopaminergic receptors specifically affects mediated responses in aversive contexts. The role of CB1 receptors on proopiomelanocortin-expressing neurons, which are essential for balancing fear and eating behaviours, was also discussed. Data on the pharmacokinetics, bioavailability and absorption of cannabigerol and its metabolite, cannabigerol-glucuronide, were presented, to assess their potential for equine clinical pharmacology. In addition, proteasomal degradation of CB1R was identified as a molecular mechanism related to cannabinoid tolerance. New therapeutic alternatives for the treatment of binge-eating disorders were also presented, including oleoilsulfamide and OLHHA, agents with anorexigenic and hepatoprotective properties. The effect of THC and synthetic THC during adolescence were also a central theme, showing their differential impact by gender on the onset of long-lasting psychotic symptoms, alterations in structural plasticity, compulsive behaviours and coping strategies, as well as their influence on the maturation of the orbitofrontal cortex and the hippocampus, key brain areas in emotional decision-making and vulnerability to addiction. These findings underline the complexity of the endocannabinoid system in the regulation of behaviour and addiction, opening new avenues for research and the development of therapeutic strategies.
This was followed by the Hot Topic, and on this occasion we were lucky enough to have Carola Pérez, president of the Spanish Medical Cannabis Observatory and founder of the association of therapeutic medical cannabis users Dosemociones, who, from her perspective as a patient, delighted us with a presentation on the current situation of medical cannabis in Spain. She told us that Spain ranks seventh in the world in the production of medical cannabis, and that thousands of patients in the country resort to this plant to treat various ailments. However, because the domestic production of medical cannabis is entirely destined for export, these patients are forced to rely on self-cultivation, user associations, or the clandestine market to access this treatment. Carola told us that self-cultivation of medical cannabis and its acquisition through third parties face numerous legal, medical, practical and social challenges. On the legal side, the lack of clear regulation and limitations on permitted quantities expose growers to possible sanctions, while products obtained in these ways often lack adequate quality controls, increasing the risk of contamination or of inaccurate dosage of cannabinoids. Cultivation requires specialised knowledge, significant financial resources and a controlled environment, compounded by the risk of theft and other security problems. On the other hand, using third parties can result in adulterated products, high costs and a lack of confidence in their origin. At the social level, there is still stigma attached to cannabis use or cultivation, which can lead to tensions with the community. Carola spoke to us about all these barriers faced by patients and highlighted the urgent need to implement a clear regulatory framework, broad enough for medical cannabis to reach all patients with adequate medical backing to ensure safe, reliable and quality access to medical cannabis.
After the Hot Topic and after the lunch break, the day continued with the fifth session of oral communications, focused on the topic of cannabinoids and cancer. It was highlighted that breast cancer, the leading cause of cancer death in women, is a heterogeneous disease in molecular, prognosis and treatment terms. In this context, the endocannabinoid system plays a key role in the response of HER2+ breast tumours, and the potential of HER2-CB2R heteromers as a new predictive biomarker was identified. The complexity of the breast tumour microenvironment, where cancer cells interact dynamically with the surrounding stroma, particularly with immune cells expressing CB2 receptors, which may have pro- or anti-tumour effects, was also addressed. This opens the possibility of considering the tumour's microenvironment as a diagnostic tool and therapeutic target in breast cancer. Finally, advances in combined cannabinoid and tamoxifen therapies were presented, which obtained superior long-term therapeutic results by forcing the differentiation of the most aggressive and chemotherapy-resistant cells, thus improving tamoxifen-mediated cytotoxicity.
The third and final day of the meeting began with the sixth session of oral presentations, focusing on papers on the metabolic syndrome. The growing interest in cannabidiol (CBD) as a treatment for metabolic diseases was highlighted, underlining the potential of nanoformulations of CBD to improve its oral bioavailability and therapeutic efficacy. In addition, evidence was presented on the use of CBD in polycystic ovary syndrome, highlighting its anxiolytic, antidepressant, anti-obesity and anti-fibrotic effects, making it a promising candidate for combining with ovulation induction therapies. Metabolic dysfunctions such as dyslipidaemia, hypertension and obesity, exacerbated by excess carbohydrates and sedentary lifestyles, which contribute to the progression of non-alcoholic fatty liver disease, were also addressed. In this context, it was shown that cannabis oil treatment prevented the increase of inflammation and fibrosis markers in a rat model of non-alcohol induced steatohepatitis.
Once again the SEIC annual meeting ended with the presentation of awards for the best publications in the field of cannabinoids by pre- and post-doctoral researchers in Spain in 2024. The predoctoral prize for the publication "The role of PPAR-γ in memory deficits induced by prenatal and lactation alcohol exposure in mice", published in Molecular Psychiatry, was awarded to Alba García Baos. The post-doctoral prize, awarded to the publication "Hydroxytyrosol linoleoyl ether ameliorates metabolic-associated fatty liver disease symptoms in obese zucker rats", published in the journal ACS Pharmacology & Translational Science, was presented to Maria Luisa de Ceglia.
Finally, to end the meeting, the prizes for the best oral communications and posters presented at the meeting were awarded, and the event was concluded following a farewell and closing words by outgoing SEIC president Dr. Cristina Sánchez.
