Therapeutic Satisfaction and Subjective Effects of Different Strains of Pharmaceutical-Grade Cannabis
Tibor M. Brunt, Marianne van Genugten, Kathrin Honer-Snoeken, Marco J. van de Velde, and Raymond J.M. Niesink
Journal of Clinical Psychopharmacoly, 2014, 34, 344Y349
Doi : 10.1097/JCP.0000000000000129
In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9- tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.
Key Words : medicinal cannabis, delta-9-tetrahydrocannabinol, cannabidiol, subjective effects, visual analog scale
Throughout history, the cannabis plant (Cannabis sativa L.) has been applied medicinally worldwide for a variety of clinical and subclinical conditions. The main pharmacologic constituents of current medicinal interest in the plant are its cannabinoids, foremost delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).1 Tetrahydrocannabinol is the main psychoactive constituent, producing cannabis’ main subjective effects for which it is renowned and which has led to its worldwide recreational use.2,3 Cannabidiol, on the other hand, seems to lack any psychoactive effects. Tetrahydrocannabinol and CBD are formed in the plant through different enzymes and enzymatic routes, both cannabinoids occur at the same time in the plant as well as their precursors.4
The pharmacodynamic mechanism underlying a major difference between both cannabinoids is the fact that they show a different interaction with the endocannabinoid receptor system in the brain; CBD binds as an antagonist to the cannabinoid receptor CB1 but with much lower affinity than THC (in fact, in the order of 9100 times less potent binding).5,6 In addition, CBD also antagonizes the action of THC on the cannabinoid G proteincoupled receptor GPR55, which is believed to be responsible for different neuromodulatory actions as the CB1 receptor.7
The effects of cannabis in humans are diverse, complex, and not yet fully understood. Alongside its well-known desirable subjective effects, such as relaxation, improved mood, and increased senses, THC is also known for causing anxiety, dizziness, depressed mood, agitation, panic disorder, and even psychosis.8,9 It is mainly these undesirable effects together with its alleged potential for dependency and illegal status in many countries that has overshadowed the possible beneficial properties of cannabis for a long time in the medical community.10,11
However, THC has been increasingly associated with medicinal effects, such as muscle-relaxing, antiemetic, analgesic, anxiolytic, appetite-enhancing, and ophthalmologic properties.1 By far, the most evidence for therapeutic efficacy for cannabinoids is in the disease multiple sclerosis (MS), where a beneficial effect on spasticity and on pain are the main reasons for treatment with cannabis.12 However, randomized controlled trials have yielded heterogeneous results and have not yet resulted in practical guidelines for the prescription of cannabis. 13 Cannabis has also been shown effective as antiemetic and in increasing appetite in patients experiencing certain types of cancer or acquired immunodeficiency syndrome, and antiproliferative and immunomodulating properties have been shown as well.1,14 Most studies describing its beneficial potential have also reported THC’s adverse effects on treatment with various cannabis extracts in patients, many of which are known adverse subjective effects of non-medicinal cannabis use as mentioned previously.3,9,15 Therefore, the current scientific emphasis lies on this precarious balance between beneficial effects and lack of adverse effects.1
Despite of this, scientific attention into the medicinal properties of cannabis has not waned over the last decade. Rather, it seems to be increasing over the years, partly because of new insights into pharmacologic mechanisms of action of nonpsychoactive cannabinoids, such as CBD.16 Cannabidiol has been suggested to have therapeutic potential in a variety of pathologies, such as inflammatory disease, diabetes, cancer, neurodegenerative diseases, and psychosis.16Y18 In fact, CBD has been shown to counteract THC’s adverse psychoactive effects in a dose-dependent fashion.19,20
Although in most countries, cannabis is considered an illegal drug, a number of countries have made an exception in the law in the case of cannabis for medicinal purposes. In The Netherlands, the Office for Medicinal Cannabis (OMC) is in charge of the cultivation of high-grade pharmaceutical cannabis for medicinal purposes.21 It is available at specialized pharmacies, and patients are advised through information brochures about the different strains of cannabis available and the methods of consumption. For instance, the OMC advises to either use a vaporizer or to prepare tea to avoid damage to the lungs. The method of administration affects the pharmacokinetics of THC. Drinking tea is associated with an enduring and mild effect, whereas inhalation causes a faster and larger delivery of THC to the blood, resulting in a higher peak value.22 However, only very small amounts of THC are soluble in boiling water.21 Currently, the OMC offers different strains of medicinal cannabis, which are cultured according to stringent pharmaceutical standards. Each strain differs in their THC content and only 1 variant contains a noteworthy level of CBD, and with this strain, the OMC advises inhalation as the only administration route because CBD is insoluble in boiling water.
Most of the scientific evidence on medicinal cannabis involve pharmaceutical cannabis products, which are orally administered or by buccal sprays, such as Sativex (GW Pharmaceuticals, Salisbury, UK) orMarinol (AbbVie, Chicago, IL). So far, only a few limited studies have been conducted on pharmaceutical-grade cultivated cannabis as medicinal therapy and have marginally described patient groups that use it.21,23,24
This study describes more than 100 patients reporting about the therapeutic satisfaction with their pharmaceutical-grade cannabis product. Furthermore, differences in subjective effects among the available strains are investigated.