Schizophrenia is a serious mental disorder affecting about 1% of the population. It is characterised by multiple symptoms which are mostly responsive to treatment with antipsychotic medications. Cognitive impairment is regarded as a core feature of illness which is mostly poorly responsive to treatment with the current antipsychotic medications. Improving cognitive function is an important treatment goal as it is associated with better outcomes in employment and quality of life. Adjunctive pharmacological treatments have been examined to improve measures of cognition but with limited success. Cannabidiol (CBD), has shown promise in preclinical models of cognitive deficits of schizophrenia. On the other hand, limited studies in small groups of patients with schizophrenia have shown no significant clinical benefits for cognitive function as an adjunct to ongoing treatment with antipsychotics. A single trial, in which CBD as a standalone treatment was compared to the antipsychotic medication amisulpride, showed significant changes in cognitive measures for both agents, with no statistically significant difference between them. It might therefore be concluded that the preclinical findings have failed to translate to the clinic. However, the preclinical findings themselves are based on a circumscribed set of studies in multiple cognitive models and have used varying doses and routes of drug administration. The same general methodological issues are present in the suite of clinical studies. Issues such as patient heterogeneity in terms of illness duration, formulation and dose of CBD employed, and length of cannabinoid treatment might militate positive findings. The limited clinical database available makes the benefits (or lack thereof) of CBD for the cognitive effects of schizophrenia uncertain. Continued research in much larger patient populations than have so far been investigated as well as a consideration of dose ranging studies are required to fully assess the potential risks against the benefits of CBD treatment for cognitive deficits in schizophrenia.

Amazingly, almost 50 years after the first demonstration of anticancer effects of cannabinoids in vitro and in vivo, well-designed clinical trials that definitively prove tumour-inhibiting effects in man are still missing. Whereas a large number of preclinical studies exist that describe tumour-inhibiting effects of cannabinoids, alone or in combination, but also in the form of medical cannabis or natural extracts in vitro, the number of in vivo studies is still limited. Even more limited are well-documented experiences in man. Most animal studies and experience with cannabinoids in man concern brain tumours. This review summarises the effects of phytocannabinoids in brain, breast, colorectal, head and neck, haematological, liver, lung, pancreatic, ovarian, prostate, and skin cancers in animal models and, if available, in patients. The large majority of animal studies demonstrate tumour-inhibiting effects of cannabinoids, thus confirming in vitro data. Experiences in cancer patients are almost exclusively limited to individual case reports and case series without a control group. Many questions are currently unanswered such as the role of pure cannabinoids compared to combinations, cannabinoids as the eventual sole cancer therapy, optimal dosages, or duration of treatment. Pure cannabidiol (CBD) seems to be superior to pure delta-9-tetrahydrocannabinol (THC) in experimental settings. The role of medical cannabis or extracts is less clear as they vary in their phytochemical composition. In conclusion, cannabis/cannabinoids may slow the progression of tumours. However, the hope that cannabinoids could eventually cure cancer as often spread in social media, is, at present, wishful thinking. Above all, well-designed clinical trials paired with long-term follow-up of cancer patients are needed.

Since the early 1970s, the U.S. Food and Drug Administration (FDA) has received over 800 investigational new drug applications (INDs) for, and pre-INDs pertaining to, research of cannabis or cannabis-derived products. The current data show that applications for research of these products submitted by both academic researchers and commercial developers focus on four major clinical areas: addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%). The product types studied have expanded greatly in recent years and include a wide variety of topical, inhalable, injectable, and oral products. In this article, the authors present a breakdown of cannabis and cannabis-derived applications received by the FDA over the past 50 years. The authors also provide a summary of their experience and challenges in reviewing applications for research of cannabis and cannabis-derived products, as well as recommendations for those interested in studying cannabis and cannabis-derived products in human clinical trials. This perspective article includes a discussion on important IND criteria, the pre-IND consultation program, drug master files (DMFs), and various guidance documents and resources. Lastly, the authors provide their perspective for the future of cannabis drug development.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can result in a range of persistent symptoms impacting everyday functioning for a considerable proportion of patients, a condition termed Long coronavirus disease (COVID) or post COVID-19 syndrome. The severity and set of symptoms vary between patients, and include fatigue, cognitive dysfunction, sleep disturbances, palpitations, tachycardia, pain, depression, and anxiety. The high prevalence of Long COVID combined with the lack of treatment approaches has resulted in considerable unmet clinical needs. There is a growing body of evidence that cannabis-based medicinal products (CBMPs) can be used to treat symptoms including pain, anxiety, depression, fatigue, sleep, headaches, and cognitive dysfunction, which are commonly reported in Long COVID. This article provides an overview of the pathophysiology of Long COVID and discusses preliminary pre-clinical, clinical trials, and real-world evidence (RWE) for CBMPs in the context of Long COVID. This review summarises current clinical trials and studies exploring CBMPs in Long COVID. The current evidence provides a rationale to further explore CBMPs as a treatment for Long COVID symptoms. In addition to further randomised controlled trials (RCTs), the increasing availability of CBMPs globally, coupled with the continued prevalence of Long COVID in the population, also highlights the value of real-world data in the research of CBMPs in Long COVID. Critically, there is an evident need for multidisciplinary approaches of CBMPs and Long COVID in real-world clinical practice settings.