A clear increase in clinic volume was observed as well as the effectiveness of the comprehensive screening process to admit eligible patients to the clinic

Recommendations for the use of safe and consistent products with certified laboratory testing and approval from the authorized regulatory agency is also essential. Following the appointment, a consultation report is sent to referring physicians including the detailed treatment plan, follow-up frequency and any specific recommendations such as monitoring of potential risk factors, adverse effects or the supervised down-titration of pharmaceutical medications.Over the years, the clinic has established a clear intervention strategy, determining the frequency and procedure for follow-up appointments and establishing well-defined monitoring tools . Both scheduled and unscheduled follow-ups occur, the latter delivered by nurses by phone or video conference. The follow-up visits serve to monitor changes to the patient’s health status and to assess treatment adherence, safety and effectiveness. Monitoring of adverse events occurs both at scheduled and unscheduled appointments, and allows for important collection, classification and reporting to pharma covigilance programs as well as required counseling for patients. Support for patient titration and, if needed, a treatment adjustment such as change in product, dosage, or route of administration takes place during the first couple of follow-up appointments. In most cases, a phone follow-up at one month, or earlier, during the titration phase is highly recommended until a stable dose is achieved. Thorough screening for completeness and eligibility of referrals has resulted in the clinic assessment of 9,102 patients during the five-year period. Fig. 3 displays the average number of patient referrals, initial visits and medical cannabis grow tray authorizations  per month in each year.

In overall assessment of the 5-year period, 67 % of patient referrals came to the clinic for an initial appointment and 82 % of those were prescribed medical cannabis . There are currently 39 % of patients under active treatment. It is of note that due to the wait time for new patients, and decrease in referrals in 2020 due to the COVID-19 pandemic, there are actually more new patients assessed  than were referred from January to March 2020. The wait time for new patients continuously increased over the years from 14 weeks in 2015 to 20 weeks in 2019. The wait time calculated between January and March 2020 was 9 weeks. The COVID-19 pandemic led to decrease in wait time for initial visit during spring 2020 to less than one month by summer 2020. A total of 54,122 appointments were recorded for 9,102 patients who were assessed and followed at the clinic between April 2015 and March 2020. Follow-ups by nurses were most predominant appointment type accounting for 41 % of total appointments, followed by nurse phone calls  and initial visits . It is clear that the clinic model depends on the nursing role, serving a critical need to provide patient education, support and monitoring between physician appointments. Importantly 61 % of clinic appointments are unscheduled follow-ups that are handled independently by the nurses via phone or videoconference and 38 % are clinic appointments at 1- or 3-month intervals with both nurse and physician. The remainder including clinical trial appointments, administrative or physician to physician consultations. As more countries implement medical cannabis access regulations, the development of dedicated medical cannabis clinics and practices is becoming a common model to address patients’ needs and gaps in healthcare professional education and acceptance.

A number of studies have examined the characteristics of patients using medical cannabis, yet, to our knowledge, no publications have yet looked at the characteristics of a clinic dedicated to medical cannabis. With less than 20 % of Canadian physicians reporting authorization  of medical cannabis over the last 20 years, medical cannabis clinics have played a critical role to support patient access.The clinic opened in Quebec in 2014, where to-date less than 4 % of physicians have ever authorized medical cannabis.The clinic’s leadership position is maintained by a commitment towards patient advocacy and healthcare professional training as well as its dedication to research and enduring ability to adapt to regulatory changes. The described clinic model offers strengths, challenges and key recommendations for development of dedicated medical cannabis clinics worldwide. The clinic model has evolved over the years and demonstrates several strengths. Patient access and advocacy remains the core service offering; the model was informed and evolved based on patients’ needs in a community setting and a conservative medical community. Notably, legalization of cannabis in October 2018 in Canada brought a significant increase in demand for medical cannabis education and an increase in referrals for patient assessment at the clinic. The experience gained by the clinic, its medical team and partners have supported an ongoing evolution in the medical community. The model of care has been adapted to other clinical settings such as out-patient clinics at hospitals. Additionally, the clinic offers support and expertise to the development of medical cannabis clinics in both community-based and institutional settings creating international impact in other countries with newly developed medical cannabis access regimes. The clinic has also developed several medical training and education programs for healthcare professionals, trainees and medical students, and currently offers an elective program for medical residents of McGill University. It offers unique on-site and virtual preceptorships for Canadian and international healthcare professionals.

Postdoctoral research fellows from Canadian universities have collaborated on short and longterm projects. Patient advocacy and education may be accelerated in a dedicated environment, with full-time medical cannabis expert personnel available for support. The clinic hosts patient education events, programs and workshops and publishes a bi-weekly patient newsletters to keep patients up to date with news articles and new clinical trials. Nurses are available for patient and medical community support via phone and email six days per week. These programs receive positive feedback from many patients. Over the years, the clinic strengthened its patient real-world data collection and opportunities to generate real-world evidence to support medical cannabis practice guidelines and clinical trial development.The patient centricity of the model and the validation of clinical information by HCPs produces high-level evidence in comparison with existing surveys resulting from a conventional model of care. There are several challenges to working in a focused practice, and many medical cannabis clinics are isolated from the healthcare community. Efforts must be made to encourage a referral from a patient’s primary or specialist care team and to provide referral reports back to referring physicians. Regular communication with health ministries, regulators and relevant professional orders is challenging but very important. The complexity of regulatory environments and required patient education can make medical cannabis care very time-intensive. Thus, it is important to develop as many efficiencies as possible and to leverage funding opportunities from the public and private sector and seek institutional partnerships where possible, to share resources. Funding may be the most significant challenge in early years, and it is recommended to expand service offering slowly as funding opportunities present. Government funds for research and development, such as Canada’s SR&D tax credit program may be accessible under well designed research frameworks. Private funding must be approached with caution to ensure ethical standards and mitigate conflict of interest. However, compliant, well-designed industry relationships for training and research services have provided critical funding to support the clinic’s initiatives.

In the absence of significant funding or in-kind support, a research program may not be possible initially, and may not be the best use of resources as challenges such as missing data, patient compliance and retention are common. However, in recent years, the clinic has found opportunities for the monetization of real-world evidence and has developed to offer services as a cannabis-focused Contract Research Organization. Operation as a clinical trial site may also provide significant funding opportunities, leveraging community relationships and providing a continuation of the objectives to support medical cannabis research and product development. Since ancient times, Cannabis has been extensively utilized by humans for a variety of uses, such as textiles, paper, food, medicine, biofuel or recreational drugs. Cannabis has been an integral part of human life since its domestication and continues into the present . However, research on the uses and applications of this plant significantly decreased and almost ceased in the mid-20th century when the species and its varieties were declared illegal in most Western countries, regardless of the concentrations of psychoactive compounds . Therefore, one of the most ancient crops, long-valued for its multiple uses, vertical grow systems for sale became largely ignored during the last 50 years. Thus, compared with other crop plants, Cannabis has not fully benefited from modern scientific technologies, which has created a major knowledge gap that remains to be filled . The last decade has witnessed a revival of interest in Cannabis research, especially in relation to the genetic and phytochemical features of the different varieties and to its evolutionary origin, domestication and further geographic diffusion . For example, the use of modern methods of molecular analysis has helped clarify the taxonomy of the Cannabis complex and its genetic modifications over time as a result of artificial  selection during the domestication process . Palynological and archeological records have been used mostly to identify the geographical center of origin of Cannabis, its center of domestication and further human-driven diffusion patterns throughout the world. Modern global and regional databases and associated handling facilities, notably geographic information system  tools, have been instrumental in this type of research . This paper briefly reviews the newly available information on the center of origin and the center of domestication of Cannabis and its further worldwide dispersal, with a focus on Europe, where spatiotemporal diffusion patterns remain controversial, and the Iberian Peninsula, which represents a knowledge gap regarding the tempo and mode of Cannabis arrival and diffusion.

Previous reviews on the subject date from roughly a decade ago . A review including the research developed on Cannabis during the last decade, which has been fundamental for setting the present standards of knowledge, is lacking. This is especially true for the meta-analyses and molecular phylogenetic investigations developed during the last five years. The present review represents an updated outlook on the evolution, domestication and worldwide diffusion of Cannabis that includes the latest developments on this topic. The review begins with a brief section regarding the current state of Cannabis taxonomy, ecology, phenology and human uses. The next section discusses the evolutionary center of origin and the time of appearance of the original wild Cannabis, followed by similar geographic and chronological considerations on Cannabis domestication and diffusion of its cultivated forms. The next section focuses on Europe, where domestication and diffusion patterns are still under discussion. The last section highlights the scarcity of information in regard to the Iberian Peninsula, in comparison with most European regions, evaluates the potential causes for this paucity and suggests how further research could contribute to bridging this knowledge gap. Time units used: Ma, million years before present; yr BP, years before present; CE/ BCE, Common Era/Before Common Era. The genus Cannabis is in the family Cannabaceae, with 11 genera and approximately 170 species. Discussions on the existence of one  or two species  started during the time of Linnaeus and Lamarck and have continued until very recently. Some morphological differences exist between the two taxa, as C. sativa is taller with a fibrous stalk, whereas C. indica is shorter with a woody stalk. There are also phytochemical divergences, as manifested in the tetrahydrocannabinol/cannabidiol  ratio, which is higher in C. indica. The discontinuous geographic ranges – the sativa lineage in Europe and the indica lineage in Asia – would also support the occurrence of two different taxa within Cannabis. The question is whether these differences qualify for defining two separate species or two sub-specific taxa. Using quantitative criteria based on key molecular DNA sequences , McPartland  concluded that the genetic differences are in the rank of subspecies and that the proper nomenclature is C. sativa subsp. sativa and C. sativa subsp. indica. Therefore, Cannabis is now considered a mono-specific genus . A number of new varieties have been obtained from these two original subspecies by artificial selection, which have different morphologies, phytochemical compositions, geographic distributions and uses .