New research from Washington State University shows that CBD inhibits nicotine metabolism. The study tested how CBD and its main metabolite 7-hydroxycannabidiol* affect cell samples from human liver tissue and other cell cultures. The mission, says Philip Lazarus, WSU professor of pharmaceutical sciences and lead author of the study, is to “reduce the harm of smoking, which is not from nicotine per se, but from all the carcinogens and other chemicals that are in tobacco smoke.”  

Study finding: CBD inhibits one of the key enzymes (CYP2A6) involved in nicotine metabolism. This means it could help tobacco users curb the urge to smoke cigarettes. Slowing the drug’s metabolism could result in delaying the craving for the next puff.   

 Even low CBD concentrations affect nicotine metabolism  

Further research has shown that over 70% of nicotine is metabolized by this enzyme (CYP2A6) in most tobacco users. The effect of CBD on CYP2A6 appears to be quite strong. The results suggest that its activity is inhibited by 50% at already relatively low CBD concentrations (1 μM).  

The same team, led by Lazarus, is currently developing a clinical trial to investigate the effects of CBD on blood nicotine levels in smokers:  

• Treatment group: smokers taking CBD 
• Placebo group: smokers taking placebo 
• Observation period: 6-8 hours    

Philip Lazarus emphasizes that further research is needed to confirm these effects in humans and to determine the dosage. But the results of the current study are already very promising.  

*Main metabolite is the substance CBD converts into in the body. 

Source:
Chem. Res. Toxicol. 2023, 36, 2, 177–187. Publication Date: January 10, 2023
https://doi.org/10.1021/acs.chemrestox.2c00259 

A twin study from the USA proves the lack of association between legalized cannabis use and the occurrence of psychiatric disorders.   

No link between cannabis legalization and psychiatric disorders 

In a longitudinal study of 4,043 North American twins, researchers from the United States and Finland found that cannabis legalization in the United States had no significant impact on a wide range of psychiatric disorders in adulthood.   

The subjects were first studied in adolescence and again between the ages of 24 and 49. They lived in states where cannabis use is legalized (40 percent) as well as those where it is prohibited.   

Another finding of the study was that the twins who lived in a state with legalized recreational use were more likely to use cannabis but, in turn, less likely to abuse alcohol or be dependent than the sibling pairs in states with cannabis prohibition.   

The study authors conclude that cannabis legalization is not associated with other “adverse outcomes” and encourage further empirical research.   

Cannabis legalization in the USA 

The U.S. has the largest population of cannabis users compared to any other country. Recreational use of cannabis for adults is already legalized in 22 states, with more to be voted on in the future. In October 2022, President Joe Biden announced that there will be sentencing relief for individuals incarcerated for simple cannabis possession – a symbolic act for U.S. states and the international community to support the decriminalization of adult-use cannabis.   

However, restrictions on the cannabis market by the federal government still exist. Regulations and laws prevent cannabis businesses from using banking services, listing on U.S. exchanges, trading across state lines, and importing or exporting products.   

Now, President Joe Biden has ordered decriminalization and a review of the legal status of cannabis. There is hope that cannabis will be reclassified for commercial sale in the near future. 

Source: 

Zellers, S. M., Ross, J. M., Saunders, G. R. B., Ellingson, J. M., Walvig, T., Anderson, J. E., Corley, R. P., Iacono, W., Hewitt, J. K., Hopfer, C. J., McGue, M. K., & Vrieze, S. (2023). Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes. Psychological Medicine, 1–10. https://doi.org/10.1017/s0033291722003762  

Headaches are among the most common types of pain in many Western countries. A new study from Canada gives hope to sufferers: cannabinoids appear to significantly alleviate the symptoms of headache patients.  

The study surveyed a total of 200 pain patients at a Calgary clinic about their use of cannabis preparations. 34 percent of respondents reported regular use – mainly in form of liquid cannabis preparations or by inhaling cannabis flowers. The preparations were used both to prevent pain and to combat acute conditions.   

Cannabis reduces pain intensity and has a preventive effect 

The results are promising: nearly two-thirds of regular users described reduced pain intensity, and about 30 percent reported that their headaches were less frequent when they took cannabinoids. The study authors concluded “a high individual benefit of cannabinoids in the treatment of headache.” In the future, they hope to see more controlled studies and a broader data base for the use of pharmaceutical cannabis in the treatment of severe headaches.
In Canada, cannabis is legalized for both medical and recreational use.   

Source:
Melinyshyn AN, Amoozegar F. Cannabinoid Use in a Tertiary Headache Clinic: A Cross-Sectional Survey. Can J Neurol Sci. 2022 Nov;49(6):781-790. doi: 10.1017/cjn.2021.215.  

The most common symptoms of arthritis include pain during daily movements and swelling of the joints. A study by U.S. researchers encourages sufferers: taking CBD appears to have positive effects on pain and physical functioning. In addition, an improvement in sleep quality was observed during therapy with medical cannabis. 

As part of the study, 428 patients suffering from joint pain were anonymously interviewed about the efficacy of CBD. Participants were recruited via social media and activities of the US patient associations “Arthritis Foundation” and “Savvy Cooperative”. The results are promising: CBD therapy is associated with improvements in pain (83 percent), physical functioning (66 percent) and sleep quality (66 percent). Especially those patients who had been diagnosed with osteoarthritis benefited from pain reduction through pharmaceutical cannabis.   

The majority of respondents also reported that their use of other pain medications had decreased or even stopped altogether as a result of taking CBD. 

The authors of the study advocate greater openness to alternative treatment options for inflammatory joint conditions such as arthritis – for example CBD therapy. In addition, further clinical studies are needed to explore the efficacy of cannabinoids in pain management for these conditions.   

source:   

Frane, N., Stapleton, E., Iturriaga, C., Ganz, M., Rasquinha, V., & Duarte, R. (2022). Cannabidiol as a treatment for arthritis and joint pain: an exploratory cross-sectional study. Journal of Cannabis Research, 4(1).

Many people who suffer from cancer have distressing symptoms such as pain and fatigue, but also  psychological complaints such as insomnia, depression or anxiety. An Israeli research team has now presented a promising prospective study with oncological patients.  The long-term study provides evidence for a reduction in the overall burden of cancer after therapy with medical cannabis. 

Structure of the cancer study 

The research group surveyed oncology patients over a total period of 2.5 years at various points in time with regard to individual pain perception, quality of sleep, sexual activity, depression and anxiety. At the beginning of the study, a total of 324 patients were involved, and the last survey was conducted with 126 individuals. The average age in the study group was 64 years, and women slightly outnumbered men, accounting for 59 percent. All participants suffered from advanced stage cancer (“Stage IV”). Breast, colon, lung and ovarian tumors were most prevalent. Therapy was with well-tolerated cannabis oils, the dosage of which was documented separately.    

Results 

The therapy with medicinal cannabis brought a significant improvement in almost all questioned aspects. The authors described the reduction in the overall burden of cancer symptoms after 6 months as particularly striking: The median decreased by 18 percent compared with baseline. Side effects were observed, but were not severe and remained stable during therapy.   

Reduction of pain symptoms, less analgesics needed 

Another interesting finding: treatment with medicinal cannabis led to a reduction in pain symptoms and less need for opiates, but also other painkillers such as non-steroidal analgesics as well as anticonvulsants or antidepressants.   

Significant improvements after 6 months of therapy 

Last but not least, the results of the study seem to indicate that the success of treatment with medical cannabis depends, among other things, on the duration of therapy. Therefore, the statistically significant changes in symptoms appeared only after 6 months of continuous intake of cannabinoids. In a previous study, the authors investigated the short-term effects of pharmaceutical cannabis therapy and found no significant improvements in cancer symptoms.  

source:   

Aviram, Joshua, et al. “The Effectiveness and Safety of Medical Cannabis for Treating Cancer Related Symptoms in Oncology Patients.” Frontiers in Pain Research, vol. 3, 20 May2022, 10.3389/fpain.2022.861037. Accessed 24 June 2022. 

Each individual has a unique endocannabinoid system (ECS) tonus that reflects the level of ECS constituents. Both, too low and too high ECS tonus levels can lead to health problems and appear to be involved in the development and chronicity of diseases. Unfortunately, the connections are largely unknown in the medical community.   

We asked Robert Uhlenbrock, a Kalapa Clinic physician and expert in the use of medical cannabis, about the importance of ECS tonus.   

CanPharma: Mr. Uhlenbrock, what happens in the human body when the ECS tonus deviates from the norm (the average values)? 

 Currently, science assumes that, for example, a clinically relevant endocannabinoid deficiency leads to an imbalance in the body’s system. This imbalance seems to be involved in a number of chronic diseases. Several studies suggest a link between low ECS tonus and irritable bowel syndrome, migraine as well as fibromyalgia complaints [1]. Especially in the development of migraine, there is increasing evidence for an involvement of the endogenous endocannabinoid system [2].    

 What are the causes for a deficiency of endogenous cannabinoids and how can this knowledge be used therapeutically? 

 Low ECS tone can have both genetic causes and be influenced by a person’s individual health behavior. For example, if the human body produces too many enzymes that break down the body’s own endocannabinoids, the tone will be too low. Since endocannabinoids play a crucial role in human physiology, deficient ECS tone can be associated with individual complaints or manifest diseases. 

 This knowledge has therapeutic relevance: If, for example, the anandamide* level in the blood were examined at regular intervals, we would notice a clinically relevant imbalance at an early stage and be able to react. I am thinking here of the intake of exogenous – i.e. plant-based – cannabinoids, but also regulation via sport, stress reduction and a healthy diet. For the so-called lifestyle factors in particular, there are now promising studies that demonstrate a health-promoting effect [3].   

 CanPharma: Why is the ECS tonus hardly considered among physicians? 

 Knowledge of the body’s endocannabinoid system is not a topic of university teaching and is therefore hardly anchored in the professional world. Whoever asks treating physicians for a determination of the anandamide level will most likely encounter little knowledge. Furthermore, as far as I know, there is no laboratory that measures this parameter as part of a blood count. The therapeutic importance of ECS the tonus is significantly underestimated. This must change urgently!  

 * Anandamide, is the best known and scientifically first described endocannabinoid. It is one of the most important endocannabinoids for controlling the balance in our body, called homeostasis. 

sources:   

[1] Russo, Ethan B. “Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.” Cannabis and Cannabinoid Research, vol. 1, no. 1, Dec. 2016, pp. 154–165, ncbi.nlm.nih.gov/pmc/articles/PMC5576607/, 10.1089/can.2016.0009. 

[2] Greco, Rosaria, et al. “Endocannabinoid System and Migraine Pain: An Update.” Frontiers in Neuroscience, vol. 12, 19 Mar. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5867306/, 10.3389/fnins.2018.00172. Accessed 23 Nov. 2020. 

[3] “Beeinflusst Sport Endocannabinoide Im Blut Und Migräne? • DGP.” DeutschesGesundheitsPortal,  25 Nov. 2021, www.deutschesgesundheitsportal.de/2021/11/25/beeinflusst-sport-endocannabinoide-im-blut-und-migraene/. Accessed 17 May 2022. 

Elderly (geriatric) patients often suffer from chronic pain and are sensitive to opiates and other centrally acting substances. A retrospective evaluation from a medical practice shows: Medical cannabis – in this case dronabinol – can alleviate the symptoms of those affected.   

Study participants included all geriatric patients aged 80 and older who were treated in a pain medicine practice in Potsdam, Germany from the time the cannabis law came into effect in March 2017 until mid-July 2018. Group A consisted of geriatric, non-palliative pain patients, group B included geriatric palliative pain patients.   

Questionnaire with information on dosages and pain intensity  

 The basis for the retrospective monocentric cohort study was a questionnaire with information on pain intensity, dosage, effects and side effects of dronabinol therapy. The results are encouraging: 21 out of 40 patients whose data were analyzed achieved a pain reduction of more than 30 percent. Another ten percent even reported an improvement of more than half. According to the respondents, about four symptoms or side effects of the previous therapy were positively influenced.  

 The authors of the study conclude from the results that cannabis-based medicines represent an effective and low-risk therapy option for the treatment of geriatric pain and palliative patients. At the same time, they call for further clinical studies – especially on the indication spectrum of the substances.   

Source:  

Wendelmuth C, Wirz S, Torontali M, Gastmeier A, Gastmeier K. Dronabinol bei geriatrischen Schmerz- und Palliativpatienten : Eine retrospektive Auswertung der ambulanten kassenärztlichen Therapie [Dronabinol in geriatric pain and palliative care patients : A retrospective evaluation of statutory-health-insurance-covered outpatient medical treatment]. Schmerz. 2019 Oct;33(5):384-391. German. doi: 10.1007/s00482-019-00408-1. Erratum in: Schmerz. 2019 Dec;33(6):562. PMID: 31473816. 

Inhaling cannabidiol e-liquid has positive effects on the verbal episodic memory of young healthy people. This was recently found by a group of Swiss researchers in a placebo-controlled study. Thirty-four people with an average age of 22 and no previous illnesses were asked to memorize 15 unrelated nouns. They were then given a single dose of CBD (12.5 mg cannabidiol e-liquid) once and once a placebo to vaporize. After about 20 minutes, they were assessed on their verbal episodic memory.

CBD outperforms placebo

The result is clear: compared to the placebo, CBD improved the short-term memory performance. The Basel research group concludes that not only does CBD have no negative effect on basic cognitive functions, they also see further evidence of the interaction of the central endocannabinoid system with vaporized CBD. In conclusion, CBD may be able to positively influence memory processes and may have further therapeutic potential if appropriate.

To investigate optimal dose-response relationships, the neuroscientists from Switzerland recommend further extensive studies.

Source: 

Hotz J, Fehlmann B, Papassotiropoulos A, de Quervain DJ, Schicktanz NS. Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial. J Psychiatr Res. 2021 Nov;143:327-333. doi: 10.1016/j.jpsychires.2021.09.007. Epub 2021 Sep 7. PMID: 34536664. 

A group of U.S. scientists from Florida has made another leap forward in terms of the effectiveness of medical cannabis for chronic pain. Analysis of Real World Data showed improvement in anxiety/depression, sleep, and quality of life.  

The Florida research team examined data of 46 adults (half of which male/female, average age 55 years) who had started treatment with medical cannabis for chronic pain. A feature of the prospective study: The survey on the factors pain intensity, anxiety/depression, sleep and quality of life took place under so-called real-life conditions, i.e. the patients transmitted their data via smartphone directly from their natural environment to the scientists.    

In order to test the effectiveness of the medication, a baseline survey, an EMA (Ecological Momentary Assessment: diagnostic access to the behavior and experience of the subjects) was conducted after one or three weeks, as well as a follow-up survey after three months towards the end of the study.   

First effects already visible after a few weeks of therapy  

The results are clear: shortly after a few weeks of therapy, the self-reported data showed a significant reduction in momentary pain intensity and a similar increase in daily sleep duration.  

After three months, a significant change in the most severe pain as well as in the depressive experience of the patients was observed. In addition, an increase in sleep duration, an improvement in sleep quality, and an increase in quality of life were observed compared to the baseline survey.   

Florida is among the fastest growing markets for medical cannabis within the United States.   

source:   

Wang Y, Jean Jacques J, Li Z, Sibille KT, Cook RL. Health Outcomes among Adults Initiating Medical Cannabis for Chronic Pain: A 3-month Prospective Study Incorporating Ecological Momentary Assessment (EMA). Cannabis. 2021 Oct;4(2):69-83. doi: 10.26828/cannabis/2021.02.006. PMID: 34671723; PMCID: PMC8525881. 

In general, they do not have a particularly good reputation: Many amoebae contain bacteria that can cause diseases in humans. A group of researchers from the Leibniz Institute for Natural Product Research and Infection Biology in Jena has now managed to pull off a trick – they have made the amoeba Dictyostelium discoideum produce a precursor of the active ingredient in cannabis, tetrahydrocannabinol (THC).   

Amoebae are single-celled organisms and are capable of producing numerous natural substances. In the case of the genus Dictyostelium discoideum – a slime mould – these are various polyketides that can be used for a whole range of therapeutic applications. These include the cannabinoid precursor olivetolic acid. The principle of action of the single-celled organisms in this respect: they join together to form larger structures that can act like a multicellular organism. 

Reactivation of slime mould enzymes 

In the course of their research, the Jena working group first found that the slime moulds produced either resveratrol (a secondary plant substance to which, among other things, an anti-inflammatory effect is attributed) or olivetolic acid, depending on the experimental set-up. The catch: the synthesis only works if a special chemical additive is present in the nutrient medium. Beyond that, the amount produced is marginal.   

In the next step, the research team developed a way to combine the slime mould enzymes with an enzyme from the hemp plant. A hybrid construct is created that is inserted into the genetic material of Dictyostelium discoideum. As a result, the amoeba directly produces the required precursor – olivetolic acid is thus produced without further additives.   

Dictyostelium discoideum acts as a production platform 

In the next step, the research team wants to produce the end product THC directly in the amoebae by introducing two more missing enzymes into the single-celled organism. A patent for the biotechnological extraction of the plant substances has already been applied for. It is particularly promising because the chemical extraction of THC in its pure form is very time-consuming, expensive and associated with low yields. Microbes, on the other hand, can be cultivated en masse and thus theoretically produce large quantities of THC in a short time. The production is not dependent on the growth of a plant or the climatic conditions. 

Original source:   

Reimer C, Kufs JE, Rautschek J, Regestein L, Valiante V, Hillmann F. Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides. Nat Biotechnol. 2022 Jan 6. doi: 10.1038/s41587-021-01143-8. Epub ahead of print. PMID: 34992245.