Side effects of cannabinoids

effets du cannabis-auswirkungen von Cannabis -Cannabis Gefahren - peligros del cannabis

Like other medicines, medicinal cannabis can cause side effects. These are mainly triggered by the active substance tetrahydrocannabinol (THC), the most important psychotropic cannabinoid. The non-intoxicating cannabidiol (CBD) is considered to be well tolerated, but can also produce undesirable effects.

Compared to many other medicines, cannabis is well tolerated: If the prescribing doctor takes into account possible risk factors and contraindications, and if patients tolerate the cannabis-based drug well, there is no risk of organ damage even in long-term therapy..

Unusual safety of cannabinoids

A major advantage of the therapeutic use of medicinal cannabis is the unusually high safety of cannabinoids compared to many other medicines. So far, no life-threatening side effects or even fatal consequences are known from the sole use of cannabis in humans. Overdoses are at best unpleasant, but at no time dangerous.

The reason for the high level of safety is that brain regions that control basic vital functions such as breathing and heart activity hardly have any cannabinoid receptors  . If medicinal cannabis is prescribed taking into account contraindications as well as risk factors and if those affected tolerate the medication well, there is no risk of organ damage for example to the liver, kidneys, stomach or brain, even with long-term treatment. To protect the respiratory tract, smoking joints is not recommended. Instead, inhalation with a vaporiser is recommended, as no combustion takes place [2].

As THC affects the cardiovascular system (tachycardia, hypotension), medical cannabis should be used with caution in patients with cardiovascular disease [3].

Cannabidiol (CBD) [4]:

Previous studies in humans have shown that CBD is well tolerated as a medicine. However, even non-psychotropic CBD is not completely free of side effects. Gastrointestinal complaints such as constipation, diarrhoea and vomiting have been observed in people receiving CBD in high doses for the treatment of epilepsies and psychotic disorders. The side effects of CBD are dose-dependent. Thus, diarrhoea and loss of appetite were observed more at higher doses. Fatigue and drowsiness also occur depending on the dosage. Other drugs that depress the central nervous system, such as antiepileptic drugs, can increase these side effects [11].

Some side effects of CBD are [4] [11]:

  • Gastrointestinal symptoms (e.g. constipation, diarrhoea, nausea, vomiting, loss of appetite and weight).
  • Fatigue, drowsiness
  • Increase in liver values

Most cannabis patients experience the effect of their drug as positive. THC and CBD reduce the sensation of pain, have a relaxing effect and increase the general feeling of well-being. How those affected experience the side effects is subjective. For example, the increase in appetite triggered by the psychotropic THC may be perceived as unpleasant in one case, while other patients seek precisely this effect.

Medical cannabis is well tolerated. Within days and weeks, a tolerance develops against many undesirable acute effects. Especially fatigue, dizziness and side effects affecting the cardiovascular system as well as the psyche decrease [3]. In the context of the accompanying survey of cannabis patients with cost coverage by the public health insurance, mainly fatigue (15.0 %) and dizziness (10.4 %) were reported [5].

Pregnancy and breastfeeding

In 2020 a scientific team from Queens University in Canada conducted a comprehensive literature review on cannabis use during pregnancy and breastfeeding and on its effect on vomiting during pregnancy (emesis gravidarum). They concluded that cannabinoids during pregnancy can lead to long-term developmental disorders in the child, some of which persist into young adulthood. In infancy, for example, hyperactivity, impulsivity and reduced attention were observed. At school age, some children develop anxious and depressive symptoms. Early initiation into cannabis use has also been observed.

Even though THC can effectively treat acute nausea and vomiting, pregnant women should not use cannabinoids. Surprisingly, there is evidence that women who used cannabis before conception suffer more from nausea and vomiting during pregnancy. Furthermore, chronic cannabis use increases the risk of developing cannabis hyperemesis syndrome [6].  For the treatment of nausea and vomiting in pregnancy, there are better-studied medicines such as antihistamines or vitamin B6 [7].

Due to the pronounced fat solubility of THC, the active substance passes into breast milk. With heavy cannabis use, the THC concentration in the milk can be one-eighth of the value in the maternal blood. THC and its degradation products are detectable in the child’s urine. Since there have been few studies on the risks for the child, most experts advise against medicinal cannabis during the breastfeeding period [6].

Medical cannabis should only be used in pregnant and breastfeeding women after careful consideration of the risk-benefit ratio..

Psychosis and schizophrenia

Heavy recreational cannabis use can, in rare cases, trigger psychosis or schizophrenia. A Swedish observational study in 1987 concluded that six percent of heavy recreational cannabis users develop schizophrenia. This seems to affect mainly people who have a genetic predisposition to develop psychiatric disorders. Cannabis use doubles the risk of psychosis in genetically predisposed individuals [8].

Research has shown that schizophrenia patients have increased levels of the endocannabinoid anandamide and a higher density of CB1 receptors in certain brain regions. This theory is supported by the fact that dopamine antagonists and the non-psychotropic cannabinoid CBD, which inhibits CB1 receptors, have antipsychotic effects [9]. Thus, if there are already known cases of psychosis and schizophrenia in the family, medical cannabis should be prescribed and used with caution. Medical cannabis should not be used in cases of severe personality disorders and psychotic illnesses, also in the medical history [4].

Psychoses have only rarely been observed in cannabis therapy accompanied by a doctor. Data from the accompanying survey (April 2017 to May 2020) of cannabis patients covered by statutory health insurance show that these side effects are rare: Hallucinations occurred in 0.8 percent, delusions in 0.4 percent and dissociation in 0.2 percent of those affected [5].

Dependence and withdrawal

Regular use of cannabis reduces the sensitivity and number of CB1 receptors that mediate the psychotropic effects of THC. Upon cessation of cannabis use, the receptors begin to regenerate after 2 days and return to normal function within four weeks [10]. After cessation of heavy cannabis use, withdrawal symptoms such as inner restlessness, increased sweating, irritability, insomnia and loss of appetite may occur [3] Smoking cannabis with tobacco is particularly problematic, as nicotine dependence develops at the same time. This increases the potential for dependence and the risk for harmful effects of cannabis [12] [13]. A study published in 2020 also showed that tobacco and cannabis users absorb significantly more harmful substances [14].

With controlled use of medicinal cannabis in therapeutic doses, withdrawal symptoms are usually not a problem [3]. In the companion survey, addiction and dependence was one of the least frequently reported side effects at 0.1 per cent [5].

Conclusion

Medical cannabis can cause side effects. However, with an individually adapted cannabinoid therapy, these are usually well manageable. In therapeutic use, a low dosage is used at first, which is increased after consultation with a doctor, depending on the relief of symptoms and tolerance, until the optimal amount is reached. Psychotropic effects of THC can also be reduced by combining it with CBD and terpenes [15].

Since medicinal cannabis has a different effect on each person, even with the same cannabinoid and terpene content, cannabis patients should find the optimal cannabinoid profile and dosage for each individual case together with the treating doctor. Close monitoring is also important: a Canadian observational study published in 2021 showed that many patients changed their cannabis medication during the course of therapy [16].

Fuentes:

[1]          Padley JR, Li Q, Pilowsky PM, Goodchild AK. Cannabinoid receptor activation in the rostral        medulla oblongata evokes cardiorespiratory effects in anaesthetised rats. Br J Pharmacol. 2003;140(2):384-394. doi:10.1038/sj.bjp.0705422

[2]          Cohen K, Weizman A, Weinstein A. Positive and Negative Effects of Cannabis and                        Cannabinoids on Health. Clin Pharmacol Ther. 2019 May;105(5):1139-1147. doi:                           10.1002/cpt.1381. Epub 2019 Mar 12. PMID: 30703255.

[3]          Das therapeutische Potenzial von Cannabis und Cannabinoiden The therapeutic potential of cannabis and cannabinoids Dtsch Arztebl Int 2012; 109(29-30): 495-501; DOI: 10.3238/arztebl.2012.0495

[4]      Cannabisbasierte Arzneimittel: Therapieoption für die Psyche Dtsch Arztebl 2021; 118(10):  A-512 / B-431 Willen, Christine

[5]          Schmidt-Wolf, G., Cremer-Schaeffer, P. 3 Jahre Cannabis als Medizin –                              Zwischenergebnisse der Cannabisbegleiterhebung. Bundesgesundheitsbl 64, 368–377                          (2021). https://doi.org/10.1007/s00103-021-03285-1

[6]          Badowski S, Smith G. Cannabis use during pregnancy and postpartum. Can Fam Physician. 2020 Feb;66(2):98-103. PMID: 32060189; PMCID: PMC7021337.

[7]          Erbrechen in der Schwangerschaft Nausea and vomiting in pregnancy Dtsch Arztebl                   2007; 104(25): A-1821 / B-1604 / C-1544 Mylonas, Ioannis; Gingelmaier, Andrea; Kainer, Franz

[8]          Müller-Vahl KR, Emrich HM. Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia. Expert Rev Neurother 2008;8(7):1037-48.

[9]          Ortiz-Medina MB, Perea M, Torales J, Ventriglio A, Vitrani G, Aguilar L, Roncero C. Cannabis consumption and psychosis or schizophrenia development. Int J Soc Psychiatry. 2018                      Nov;64(7):690-704. doi: 10.1177/0020764018801690. PMID: 30442059.

[10]        Bonnet U, Preuss UW. The cannabis withdrawal syndrome: current insights. Subst Abuse Rehabil. 2017;8:9-37 https://doi.org/10.2147/SAR.S109576

[11]        Huestis, Marilyn A et al. “Cannabidiol Adverse Effects and Toxicity.” Current                                    neuropharmacology vol. 17,10 (2019): 974-989. doi:10.2174/1570159X17666190603171901

[12]        Nutt D, King LA, Saulsbury W, Blakemore C. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 2007 Mar 24;369(9566):1047-53. doi:10.1016/S0140-6736(07)60464-4. PMID: 17382831.

[13]        Hindocha C, Shaban ND, Freeman TP, et al. Associations between cigarette smoking and cannabis dependence: a longitudinal study of young cannabis users in the United Kingdom. Drug Alcohol Depend. 2015;148:165-171. doi:10.1016/j.drugalcdep.2015.01.004

[14]        Meier, Ellen et al. “Cigarette Smokers Versus Cousers of Cannabis and Cigarettes: Exposure to Toxicants.” Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco vol. 22,8 (2020): 1383-1389. doi:10.1093/ntr/ntz199

[15]        Boggs DL, Nguyen JD, Morgenson D, Taffe MA, Ranganathan M. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology. 2018;43(1):142-154. doi:10.1038/npp.2017.209

[16]        Kalaba M, MacNair L, Peters EN, Eglit GML, Rapin L, El Hage C, Prosk E, Ware MA.                          Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec. Cannabis Cannabinoid Res. 2021 May 10. doi: 10.1089/can.2020.0140. Epub ahead of print.     PMID: 33998902.

About Minyi Lü

Minyi Lü leidet an chronischen Schmerzen aufgrund ihrer Fingerarthrose. Ihre Beschwerden behandelt sie seit 2017 sehr erfolgreich mit medizinischem Cannabis. Als Pharmazeutin im Praktikum bringt sie nun ihr Know-how ein, um über die neuesten wissenschaftlichen Erkenntnisse rund um Medizinalcannabis zu berichten.

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