Updates

With wars still raging around the world, many people live in fear and uncertainty. These experiences can lead to Post-Traumatic Stress Disorder (PTSD). While therapy and medication can help, they don’t work for everyone. That’s why more people are exploring alternatives—like cannabis. Once mainly known as a recreational drug, cannabis is now being taken more seriously as a possible treatment. In this article, we explore whether cannabis could help people with PTSD and what science has to say about it.

What is PTSD and how is it treated?

PTSD can develop after experiencing or witnessing a traumatic event. It is characterized by flashbacks, nightmares, trouble sleeping, hyperarousal and avoidance of places, people, or situations reminding of the trauma¹. Around 3.9% of the global population will experience PTSD at some point in their lives². However, the rates are much higher among those exposed to violent conflict or war (15.3%)². PTSD is typically treated with a combination of psychotherapy and prescription medication. Unfortunately 40-50% of individuals don’t respond to current treatments³.

Can cannabis be a treatment option for PTSD?

In recent years, cannabis-based medicinal products have gained attention as a potential new treatment for PTSD. The focus is on the body’s endocannabinoid system (ECS), which plays a role in regulating stress, emotional memory, and the processing of fear—all important factors in PTSD. Compounds in cannabis, particularly THC (tetrahydrocannabinol) and CBD (cannabidiol), interact with this system, which has led researchers to wonder whether these substances might ease PTSD symptoms⁴.

What does research say about cannabis & PTSD?

So far, research on cannabis for PTSD is still limited. A recent meta-analysis, which included only ten studies, showed mixed results: about half of the studies reported therapeutic benefits, while the other half found no effect or even a worsening of symptoms⁵. The most promising results were seen in improved sleep and fewer nightmares.

What about real-world data?

There is growing interest in using Real-World Data (RWD)—information gathered from actual clinical practice, such as electronic health records or patient surveys⁶. One recent study followed 269 people diagnosed with PTSD for up to 18 months⁷. Participants reported improvements in PTSD symptoms, anxiety, sleep, and quality of life. However, it is important to note that 74% of the participants were already using cannabis when the study began, which may have influenced the results.

So what can we conclude about cannabis & PTSD?

At this time, there is no strong scientific evidence supporting cannabis as a reliable treatment for PTSD. Most studies so far have focused on male military personnel and veterans, making it also unclear whether the findings apply to women or people who have experienced other types of trauma. Additionally, many of the studies are observational, meaning they cannot show whether cannabis is more effective than a placebo or standard treatments. More high-quality research—including well-designed clinical trials and real-world data—are needed to determine whether cannabis is a safe and effective long-term treatment option for PTSD.

References

1. American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.)
2. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017 Oct;47(13):2260–74. doi:10.1017/S0033291717000708.
3. Green B. Post-traumatic stress disorder: new directions in pharmacotherapy. Adv Psychiatr Treat. 2013;19(3):181–190. doi: 10.1192/apt.bp.111.010041
4. Hill, M., Campolongo, P., Yehuda, R. et al. Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder. Neuropsychopharmacol. 43, 80–102 (2018). https://doi.org/10.1038/npp.2017.162
5. Rodas, J. D., George, T. P., & Hassan, A. N. (2024). A systematic review of the clinical effects of cannabis and cannabinoids in posttraumatic stress disorder symptoms and symptom clusters. The Journal of clinical psychiatry, 85(1), 51827.
6. Real-World Evidence—What Is It and What Can It Tell Us? The New England Journal of Medicine, Dec. 6, 2016
7. Datta, A., Erridge, S., Warner-Levy, J., Clarke, E., McLachlan, K., Coomber, R., … Sodergren, M. H. (2025). UK medical cannabis registry: an updated clinical outcomes analysis of patients with post-traumatic stress disorder. Expert Review of Neurotherapeutics, 25(5), 599–607. https://doi.org/10.1080/14737175.2025.2490539
8. ∆-9-THC (THC): delta-9-tetrahydrocannabinol; CBD: cannabidiol.
9. Other relevant, topical, cannabinoids include ∆-8-THC which is derived from CBD through chemical industrial process.
10. WHO. ICD-10. Intoxication is a transient condition that follows the administration of a psychoactive substance and results in disturbances in the level of consciousness, cognition, perception, judgement, or behaviour, or other psycho-physiological functions and responses.
11. Lynskey, M. and W. Hall, The effects of adolescent cannabis use on educational attainment: a review. Addiction, 2000. 95: p. 1621-1630.
    Fergusson, D. and J. Boden, Cannabis use and later life outcomes. Addiction, 2008. 103: p. 969-976.
    Iversen, L., Cannabis and the brain. Brain, 2003. 126: p. 1252-1270.
    Di Forti, M., et al., High-potency cannabis and the risk of psychosis. British Journal of Psychiatry, 2009. 195(6): p. 488 – 491.
    Frisher, M., et al., Assessing the impact of cannabis use on trends in diagnosed schizophrenia in the United Kingdom from 1996 to 2005. Schizophrenia Research, 2009. 113(2-3): p. 123128.
    Fergusson, D., et al., Cannabis and psychosis. BMJ, 2006. 332: p. 172 – 175.
    Burggren, A., et al., Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives. Am J Drug Alcohol Abuse., 2019. 45(6): p. 563–579.

She still remembers her first cannabis order ten years ago, receiving three 5-gram pharmacy containers of Bedrocan® flos. “I was nervous. Now, I have dispensed over 20,000 cannabis-based medicine preparations, most as oil extracts for oromucosal administration.” The number continues to grow annually. The speaker is Italian pharmacist Annunziata Lombardi. She is one of the healthcare professionals who have been interviewed for ‘The clinical primer’, a publication especially intended for doctors and pharmacists who want to learn more about the administration of cannabis as a form of therapy. Below you will find a summary in which Lombardi focuses primarily on the dosage and application of medicinal cannabis in patients.

Can you describe a typical patient to whom you would dispense cannabis-based medicines?

There is no typical patient because cannabis-based medicines can be used for all age groups and for multiple pathologies. The Italian National Health Insurance reimburses cannabis-based medicines, as magistral prescription preparations, for a limited number of medical indications: anorexia/cachexia, glaucoma, Tourette syndrome, spasms and pain induced by chemotherapy, vomiting and lack of appetite in chemotherapy patients. In my experience, the most recurrent diseases are chronic pain, fibromyalgia, and neurological problems. There is also a growing demand from patients suffering from autism, anxiety, and sleep disorders.

Oral dose forms (oil extracts) are an increasingly popular mode of administration, what advice do you give patients on safe use?

In Italy, cannabis extracts, for oromucosal dosing, account for 80% of prescriptions. I train my patients on the proper dosage to convert the mg of active substance (THC and CBD) prescribed by the physician into mL and/or drops of extract. This conversion is different for every extract, and it is based on the post-extraction HPLC analytical results. In Italy, pharmacists must analyse the extract for cannabinoid content after production and state this on the label before dispensing. This helps the patient know the amount of active substance taken.

What advice do you give patients on vaporization?

I recommend the use of a medical device because it guarantees the quality and reproducibility of the therapy. However, some patients cannot afford a medical device and opt for another type of vaporizer. In any case, I ask the patient to pay attention to two aspects: (1) the vaporizer temperature, because naïve patients may experience major side effects if the temperature is set too high, (2) the timing of the onset of action, which can be extremely rapid with this administration route.

What do patients say about the administration of cannabis-based medicines by vaporization?

Patients who need an immediate effect to control tremors, intense pain, and seizures appreciate the rapid onset of action provided by inhalation. The main disadvantages of this route are: it is not discrete and often cannot be used in public spaces; the cost of the vaporizer is high; some patients do not have the pulmonary power to actively inhale.

What special considerations should pharmacists be aware of for patients taking oral dose forms?

Pharmacists must inform the patient that the onset of the oral dose form is slow and can take up to three hours. The patient must be aware of that and wait for the effect and not take additional medicine.

Do you have any good advice for pharmacists starting out?

Be passionate about what you do. This is an exciting professional opportunity and it is nothing like dispensing finished drugs.

• Be convinced that you are part of the cannabis- based medicines revolution and this is just the beginning.
• Go to cannabis conferences and trainings in your country and abroad if you have the chance.
• Read scientific literature. There is a lot of academic and clinical research going on.
• Collect patient’s feedback and data.
• Look for other professionals who share your interest. Do not stop at pharmacists but look for physicians, scientists, patients, and anybody who can help you enrich your knowledge.
• Build up strong and solid relationships with physicians and patients.

In addition to the cannabis product Bedrocan® (22% THC | < 1% CBD), Bedrocan has launched two new standardised cannabis products for compounding pharmacies in Australia: Bedropuur® and Bedrolina®. As of this year, these cannabis active pharmaceutical ingredient (API) products will be grown especially for the Australian market in Bedrocan’s brand new EU-GMP-certified production facility in Denmark. All these products will be available in flos and cut flos (ground, dried flower) forms in various packaging configurations.

Compounding pharmacies can use these cannabis API products to tailor cannabis medicines to patients’ individual needs. These products can be supplied in 400 or 3.000 grams packaging.

Cannabis for patients

Doctors can also prescribe these new medicinal cannabis products directly to patients. The Australian distributor Novachem delivers the products in 10-gram packages directly to pharmacies for patient use. These products can be administered by inhalation through a medical vaporizer offered by Storz & Bickel. The already available product Bedrocan® can also be administered using the metered-dose SyqeAir inhaler, a medical device developed by Syqe Medical, which contains Bedrocan® flos in its EU-GMP-certified cartridges.

*) Chemovar – a distinct species of Cannabis sativa L. defined by the chemical profile of its cannabinoids and terpenes.

Oral dosage form

Bedrocan is currently developing a new Bedrocan® oral dose form with different THC: CBD ratios. The plan is to launch these products later this year in different markets, including Australia. Additionally, the company is currently finalising the development of a new dose form for inhalaton, that will be initially available as a compounding product, and later potentially as a finished product. In 2026, other chemovars, such as Bedrobinol® and Bediol®, can also be supplied from Denmark to Australia, depending on the demand.

The UMC Utrecht Brain Center, in collaboration with various organisations in the Netherlands, will conduct research into the effects of adding CBD cannabis oil to the treatment of children with treatment-resistant epilepsy. The study drug to be administered is the Bedrolite® CBD oil from the  Dutch Transvaal pharmacy. This medicinal oil is made from Bedrocan’s cannabis. The research group has been allocated 1.4 million euros from ZonMW s Good Use of Medicines programme, which funds research in the Netherlands. The research will take about four years.

A total of 50 patients can participate in the study. Importantly, the patients have not previously used Bedrolite® CBD oil to treat epileptic seizures. In the first instance, the medicine’s effect on the attacks is examined, which is why participants must have a minimum of eight attacks every four weeks. Otherwise, the effectiveness cannot be assessed.

The study has started in 2025.

Lead researcher Floor Jansen hopes that after the research, neurologists can better predict for which patients CBD (cannabidiol) is an effective treatment. You can read more about this on the UMC’s website. Jansen: “Our research focuses on the individual. Instead of looking at a group, we look at whether the drug is effective per patient. We want to investigate whether the number of attacks decreases, but we also pay attention to other important outcomes for a patient. Think of less use of emergency medication against prolonged attacks, a change in alertness or a better night’s sleep.”

Call for doctors

Practitioners of children with epilepsy who would like to know more about the study can contact Floor Jansen, pediatric neurologist at UMC Utrecht (via the secretariat of pediatric neurology at UMC Utrecht, Netherlands).

The quality of CBD oil, and other CBD products, on the global market varies greatly. From pharmaceutical quality, prescription medicines, to those which are of dubious quality, and in some cases outright dangerous.

There has been a lot of interest, and indeed, investment in cannabidiol (CBD). This is partly because, unlike THC, it is not intoxicating. [1] [2] It has also been re-scheduled in a number of countries, permitting use as a prescription medicine. [3] [4] In the background of regulatory change, CBD has been showcased globally as a wonder drug – almost a panacea.

The rise in use of CBD oils, or any other product containing CBD, reflects a sharp rise in self-medication. The trend is underscored by the population risk of taking high doses of a medicine we still know very little about. [5]

The rise of CBD oils

A video about a young named Charlotte Figi ignited a storm – the online report went viral. ‘CBD oral dosing reduced a young child’s epileptic seizures brought on by Dravet syndrome.’ [6] [7] [8] Media coverage increased CBD oil demand, [9] while political power plays promoted accessibility. [10]

While anecdotal reports sparked interest cannabinoid treatments, the lack of clinical evidence did not support safety or efficacy. Subsequently, GW Pharmaceuticals published solid research supporting the use of CBD in treatment resistant epilepsy (i.e. Dravet syndrome and Lennox-Gastaut Syndrome). Epidiolex™ then received FDA approval. [11]

In the background, rapidly moving away from the epilepsy focus, CBD was gaining momentum in other conditions. With the great promise of its therapeutic potential, combined with the lack of regulatory oversight, a huge, worldwide market for (unregulated) CBD products has emerged. [12]

Unregulated, or poorly regulated products are a problem for consumers and patients alike. The cannabinoid composition may not be correctly disclosed, nor checked by a certified control laboratory. Products may contain no CBD at all, while others may contain high doses of THC. [13] Such dubious products may also include residual manufacturing solvents, and contaminants such as microbes, pesticides, heavy metals or mycotoxins.[14] Besides posing a health threat to consumers, the lack of product consistency makes it difficult to evaluate the therapeutic effects. [15]

The demand for CBD is expected to markedly increase if CBD becomes available for use as wellness products (e.g. lotions, balms, oral drops), and, or is incorporated into consumer products (i.e. beverages and other food stuffs). This trend may be partly driven by the might of the alcohol industry, with the likes of Constellation Brands (an alcohol company) and Canopy Growth Corporation (a Canadian recreational/medicinal cannabis producer) weighing into the market. [16]

Can CBD be harmful?

There seems to be a global concensus that CBD is safe, without harm. Perhaps this is driven by that it is not intoxicating, alongside its relative success certain specific cases.

The FDA are deliberating this very issue “there are many unanswered questions about the science, safety, and quality of products containing CBD”. [17] As such, if CBD is shown to be a risky substance, causing harm such as toxicity to the liver, the entire industry that has invested so heavily in it will fall under heavy scrutiny. Many companies could fail.

CBD is a medicine, so always consult a doctor

Given CBD affects the endocannabinoid system, it can also disrupt that system. There are also many unknowns about CBD, especially about the long term use and in high daily doses. [18] [19]

Side effects from CBD

Some side effects from CBD might include fatigue, diarrhoea, decreased appetite, and weight loss. [20] [21] Furthermore, CBD is typically an adjunct treatment (taken with other medicines) and is metabolised by the liver cytochrome P450 enzymes (CYP450). When taken together with other medicines metabolised by the CYP450 system, there is the potential for drug-drug interactions. [22] Finally, dose adjustment is recommended in patients with moderate to severe hepatic impairment, to reduce burdening the metabolic process. [23]

Widespread ‘self-medication’ poses risks beyond poor quality products. Consumers or patients should be encouraged to ask about or inform health professionals before trying CBD. Health professionals should suggest using only reliable, safe and standardised products, preferably of pharmaceutical quality. Typically, this would mean accessing products from a pharmacy.

A reputable CBD oil, or any CBD product, will have a Certificate of Analysis (CoA) to confirm the label claimed CBD content (milligrams per millilitre (mg/mL)), and that it is free of contaminants. A CoA is produced by an external, independent contracted laboratory. Ask for this. [24] A quality product is also likely to have online reviews, which can be compared with the CoA.

Most CBD oils are not approved

CBD products (oils, capsules, ontments) can be purchased online, are distributed through informal cannels, or from the drug store. In Europe and the USA, many are sold as a food supplements, with most not having been approved by the European Food Safety Authority (EFSA) or Food and Drug Administration (FDA).

Good quality CBD products

Quality control and standardisation of the cannbis being used is very important. The use of sub-standard materials and methods to produce CBD medicine, for example, risks batch-to-batch variation and the potential for medicine contamination (i.e. toxicity) [25] [26] [27] [28] [29]. Good quality CBD products are produced by pharmaceutical companies, or a compounding pharmacy. The manufacturing process assures consistent strength, purity and the monitoring of the manufacturing operations. Unregulated producers cannot assure consumers and patients this level quality.

In sum, there is a dire need to confirm the clinical value of CBD, as well as to properly regulate its quality and distribution as a potential medicinal product.

References

[1] Kowal, M., Hazekamp, A., Colzato, L., van Steenbergen, H., Hommel, B.. (2013). Modulation of cognitive and emotional processing by cannabidiol: the role of the anterior cingulate cortex. Frontiers in Human Neuroscience. 7

[2] Mechoulam, R., Parker, L., Gallily, R. (2002). Cannabidiol: An Overview of Some Pharmacological Aspects. The Journal of Clinical Pharmacology. 42(S1):11S-19S

[3] For example, New Zealand currently permits CBD as a prescription medicine, while Australia is currently considering low dose CBD as Pharmacy Only Medicines.

[4] Despite its widespread use, CBD remains a controlled drug. The UN Single Convention 1961 lists cannabis and preparations in Schedule I (extracts and tinctures) and IV (cannabis and resin). Given CBD is derived from cannabis, it is a controlled drug.

[5] WHO (2018). Cannabidiol critical review report. WHO Expert Committee on Drug dependence. Geneva; June 2018. . Retrieved online 28 October 2020

[6] Marijuana stops child’s severe seizures. Retrieved online 28 October 2020

[7] Charlotte’s Web CBD products: 2020 review. Retrieved online 28 October 2020

[8] Charlotte’s Web. Retrieved online 28 October 2020

[9] Example. Epilepsy patients flock to Colorado after medical pot gives them hope. Retrieved online 28 October 2020

[10] Example. Medicinal cannabis: Victorian families hopeful as state grows crop to treat children with severe epilepsy. Retrieved online 28 October 2020

[11] FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy.U.S. Food and Drug Administration. Retrieved online 28 October 2020

[12] Dance, a. (2019).  As CBD skyrockets in popularity, scientists scramble to understand how it’s metabolized. Nature magazine on November 14, 2019. Retrieved online 28 October 2020

[13] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[14] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11

[15] Freeman, T., et al. (2019). Medicinal use of cannabis based products and cannabinoids. BMJ 2019;365:l1141

[16] What Constellation Brands’ massive investment in Canopy Growth Corp. means for both companies. Retrieved online 28 October 2020.

[17] FDA consumer updates. What you need to know (and what we’re working to find out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD. Retrieved online 28 October 2020

[18] Ibid.

[19] Huestis, M., et al. (2019). Cannabidiol adverse effects and toxicity. Curr Neuropharmacol. 2019 Oct; 17(10): 974–989

[20] Epidiolex. Highlights of prescribing information. Retrieved online 28 October 2020

[21] Iffland, K., & Grotenhermen, F. (2019). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017; 2(1): 139–154.

[22] Lucus, C., et al. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol (2018) 84 2477–2482 2477

[23] Ibid

[24] See this reference for advice. Chesak, J., (2019). Reading a CBD label: How to find a quality product. Retrieved online 28 October 2020

[25] Hazekamp, A. An evaluation of the quality of medicinal grade cannabis in the Netherlands. Cannabinoids 2006;1(1):1-9

Compared to pharmaceutical cannabis, non-pharmaceutical cannabis has been found to contain less cannabinoids, is contaminated with bacteria and fungi, and often will contain the pesticides, fungicides or heavy metals.

[26] Bettiol et al. (2019). Galenic preparations of therapeutic Cannabis sativa differ in cannabinoids concentration: A quantitative analysis of variability and possible clinical implications. Front. Pharmacol., 17 January 2019 |

[27] Calvi, L., et al. (2018). Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and macerated oils based on HS-SPME coupled to GC-MS and LC-HRMS (q-exactive orbitrap®) approach. J Pharm Biomed Anal. 2018 Feb 20;150:208-219

[28] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[29] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11

Bedrocan is bringing new opportunities for the nutraceuticals industry at Vitafoods Europe 2025 with its new high-CBD cannabis product. The recently introduced Bedrolina® can be used as biomass for manufacturing different nutraceutical products, including food supplements. The consistent cannabinoid content of Bedrolina® supports cost-effective and high-quality production of CBD-based formulations. The material contains up to 14% CBD and less than 1% THC and is available in cut flos form (ground, dried flower) and in whole-dried flower form.

CBD raw materials

In recent years, CBD products have become popular in nutraceuticals as more jurisdictions regulate CBD across the globe. However, the options for reliable cannabis raw materials with high CBD levels and consistent supply seem limited. This creates a challenge for manufacturers to keep a qualitative production process.

Due to regulatory barriers, hemp varieties are the most common source of supply for manufacturers of CBD-based products, as these contain a maximum of 0.3% THC. According to Bedrocan’s CEO, Jaap Erkelens, these hemp-derived raw materials are not the best option for nutraceutical manufacturers: “Hemp varieties often contain a lower CBD percentage, which means that more biomass is needed. In addition, these hemp varieties are not suitable for medicinal applications.”

Besides the advantage of using less plant material, manufacturers will also be able to rely on a consistent supply of this non-hemp CBD variety from our new facility in Denmark, an important advantage in a market with growing demand.

Outdoor cultivation

The company has also started an outdoor cultivation project, growing high-CBD and other novel medicinal plants through a partnership in Suriname, which may become another option to supply the nutraceuticals industry in the future, especially in the North and South American regions. Additionally, Bedrocan also presents its contract manufacturing services knowledge transfer to other herbal raw material suppliers at Vitafoods Europe 2025.

Cannabidiol, abbreviated as CBD, is a cannabinoid and is only found in the cannabis plant. CBD is getting a lot of attention, and everyone knows someone who uses it. But what is CBD, and how does it compare to the other cannabinoid THC? And what is it used for?

There are currently more than 100 different identified cannabinoids, of which THC is the best known. CBD and THC are very similar in their chemical structure but have very different effects.

Can you get high from CBD?

CBD has medicinal properties but cannot make the user feel ‘high’. THC can. Some studies suggest that CBD may be effective in treating symptoms of rheumatoid arthritis, diabetes, PTSD, anxiety disorder, and antibiotic-resistant infections, among others.

CBD and epilepsy

More recently, CBD has been used in children with treatment-resistant epilepsy, and a subsidy has been made available by the Dutch government for further research. This study will not only look at CBD, but cannabis products in general, including THC.

THC is more likely to be used to reduce nausea, vomiting, pain and muscle spasms and improve sleep and appetite and the scientific evidence for its effectiveness in these conditions is more sound than the one available for CBD.

Ideal THC:CBD ratio

It has been shown that CBD can influence the effects of THC. However, it is still difficult to say which THC:CBD ratio is the most ideal for a specific medical condition. As an example, a study into the pain experienced by fibromyalgia patients showed that the combination of CBD and THC had a better effect on pain reduction than a product with THC alone. Conversly, CBD alone had no effect on pain. In a follow-up study, the researchers are now looking if a THC:CBD balanced ratio cannabis is better than opiates in reducing  fibromyalgia pain.

However, the ultimate medicinal effect of cannabis does not depend solely on CBD or THC.

Terpenes refine the therapeutic effect

Terpenes are the substances that give cannabis its characteristic smell and taste. So far, over 120 different terpenes have been found in cannabis, with unusual names such as myrcene, alpha-pinene and beta-caryophyllene.

Unlike cannabinoids, terpenes can be found everywhere in nature. For example, they are present in lavender, roses and pine trees. Some studies suggest that terpenes may counteract certain undesirable effects of THC, such as feelings of restlessness or loss of short-term memory, although thorough research on this topic is still lacking.

Certain terpenes may also have medicinal properties of their own: some are antibiotics, while others have analgesic or anti-inflammatory effects. Terpenes are therefore often used in aromatherapy.

Because there are many different terpenes, there are also many different combinations in which they can occur in a cannabis plant. As with cannabinoids, each specific mix of terpenes can lead to a unique medicinal effect. The terpenes are suspected to work with cannabinoids to modify or amplify their effects. This is known as the ‘entourage effect’.

Acidic and neutral cannabinoids

THC and CBD are not present in the cannabis plant in ready-to-use form but must first be heated to a temperature of at least 180°C.

The plant only contains ‘acidic’ cannabinoids. THC is, therefore, primarily THC acid (THCA), and CBD from the plant is CBD acid (CBDA, also known as cannabidiolic acid). When these substances are sufficiently heated, the cannabinoid acids are converted into a neutral form known as THC and CBD. This chemical process is called decarboxylation.

Decarboxylation also occurs spontaneously in cannabis as a result of exposure to light and room temperature, although at a slower pace. However, cannabis can be kept for a very long time in the freezer.

CBD acid

Until recently, scientists thought that the acidic cannabinoids had no medicinal properties. However, these substances can indeed be interesting as medicines. For example, it appears that CBDA bactericidal properties and seems promising as an anti-inflammatory substance. Additionally, THC acid seems to have a strong effect on the human immune system.

The actions of CBD

The human brain and other organs contain naturally occurring cannabinoid (CB) receptors and the chemicals that bind to them. This is called the human endocannabinoid system. CBD, by comparison to THC, has less affinity for the CB1 and CB2 receptors and works to partly block receptor activity (as a partial antagonist). CBD displays high potency as an antagonist of CB1 and CB2 receptor agonists in CB1- and CB2-expressing cells or tissues. Furthermore, CBD inhibits the uptake and hydrolysis of the endocannabinoid anandamide (AEA), thus increasing its concentration in the tissues where it is produced. CBD has been identified as a serotonin receptor (5-HT1A) agonist, which may be the basis of its purported anxiolytic and antipsychotic actions. [1-4]

References

1. Davies, and S. Bhattacharyya, Cannabidiol as a potential treatment for psychosis. Ther Adv Psychopharmacol, 2019. 9: p. 1–16.
2. Crippa, J., et al., Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. . Front Immunol, 2018. 9: p. 1-16.
3. Campos, A. and F. Guimarães, Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl), 2008. 199: p. 223-230.
4. Zanelati, T., et al., Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br J Pharmacol, 2010. 159(1): p. 122-8.

The way the cannabinoids THC and CBD move through the body (pharmacokinetics) varies depending upon how it is taken. The duration of their action is influenced by dose size, dose form, and the route of administration – the lungs, mouth, gut or the skin.

Cannabinoids – absorption and distribution

THC and CBD are mainly found in cannabis in their inactive acid form THCA and CBDA. To activate THC and CBD a carboxyl group must be removed by heat. In practice, this so called ‘decarboxylation’ occurs by heating cannabis in a vaporizer, or heating the cannabis extracts before being placed into a solution.

The absorption of inhaled cannabinoids results in a maximum (peak) blood concentration within minutes (see figure). Effects in the brain start within seconds to a few minutes, and reach a maximum after 15-30 minutes. They taper off within 2-3 hours.

Absorption is slower when cannabinoids are ingested. Lower, more-delayed peak concentrations occur with oral ingestion. The effects in the brain are delayed for 30-90 minutes, and reach their maximum after 2-3 hours. They last for about 4-12 hours.

Bioavailability of cannabinoids

Bioavailability describes the proportion of a medicine entering blood circulation after administration. The bioavailability of oral THC and CBD is low. By comparison, the inhalation of cannabinoids has been shown to be more effective and reliable compared to oral administration.

THC and CBD are fat soluble (highly lipophilic) compounds which are rapidly absorbed by the lungs. As a result, inhalation is a convenient and fast-acting method of administration, allowing easier titration to the desired dosage and biological effect. About 25% of inhaled THC enters the blood circulation.

The distribution of cannabinoids in the body are ruled by their lipophilicity (their fat solubility) and binding to blood proteins. THC is distributed widely throughout the body, particularly to fatty tissues. The body storage of THC increases with increasing frequency and duration of use.

Metabolism and elimination of cannabinoids

The cannabinoids are mainly metabolised by a collection of liver enzymes called cytochrome P450 (CYP450). The same as many other medicines, these enzymes chemically alter the cannabinoids to remove them from our body (excretion). Besides the liver, other tissues like the heart and lungs are also able to metabolise cannabinoids, albeit to a lesser degree. THC and CBD metabolism follows a similar metabolic route.

Elimination of medicines means their complete removal from our body. Metabolism is the major route for the removal of THC. Unlike THC, a large proportion of CBD is excreted unchanged. Within 5 days of taking a single dose, a total of 80−90% of THC is excreted. The elimination of THC and its metabolites occurs via the faeces and urine. After inhalation, about 25% of the absorbed dose is excreted in the urine; about 65% is eliminated via faeces.

Only very small amounts of THC are excreted unchanged. Less than 5% of an oral dose is found unchanged in the faeces. THC metabolites can be found in the urine and faeces for several weeks. The slow elimination of cannabinoids and their metabolites is due to their slow movement out of our body fat and other tissues back into the bloodstream.

The new Danish production site recently passed a GMP inspection, carried out by the Danish Medicines Agency DKMA, with flying colours. The Danish authorities have now granted the GMP certificate that allows Bedrocan to start cultivation. The Bedrocan board of directors would like to congratulate all employees involved in achieving this enormous milestone. The cultivation activities are now in full swing to supply the first customers in 2025. The recruitment of new staff, including processors and packers, will also start shortly.

First audit

“The fact that the inspectors were satisfied with their first audit makes it something very special for us as a company and our industry. The fact that our Dutch knowledge and experience has been transferred 1-on-1 to another jurisdiction is evidence of an unparalleled level of professionalism,” CEO Jaap Erkelens proudly explains. Bedrocan is a cannabis grower of Dutch origin who, in addition to two cultivation locations in the Netherlands, has also delivered a brand new facility in Køge (Denmark) and is now also working on breathing new life into the former production facility in Canada. ‘I am convinced’, Erkelens continues, ‘that we can once again use this Danish experience elsewhere in the world as the Bedrocan concept for cannabis medicines.’

Annual capacity

The certificate was obtained just before the end of 2024 and the staff could not have imagined a better way to end both the year and the project. The Danish facility will aim to meet the growing demand for Bedrocan’s standardised medicinal cannabis. The new production location has an annual capacity of 2,300 kilos.

A recent study conducted by the Leiden University Medical Center (LUMC) examined the side effect profiles of the opioid oxycodone and cannabis product Bediol®. The outcomes of the study were published in the scientific journal Frontiers in Pain Research under the title Cannabis Combined with Oxycodone for Pain Relief in Fibromyalgia Pain: A Randomized Clinical Self-titration Trial with a focus on Adverse Events.

The results showed that (i) around one in four participants dropped out of the study, mainly due to the severity of adverse effects experienced from inhaled cannabis; (ii) there were no significant differences in pain scores between treatments; (iii) the drug load increased in patients treated with the combination of oxycodone and cannabis relative to either treatment alone; and (iv) patients titrated their dosing based on adverse effects and pain relief.

Bedrocan’s Chief Scientific Officer, Mikael Kowal, briefly commented on the results: “Unfortunately, the results are not entirely as expected. We hoped that Bediol® would provide clear advantage over oxycodone in terms of the side effect profile and treatment efficacy for fibromyalgia-induced pain. However, due to many patients not tolerating inhaled cannabis well, the study results do not clearly point to a beneficial effect of Bediol®. To be precise, 31% of patients that received cannabis dropped out from the study due to various adverse effects, most notably headaches.”

Cannabis or opioids for pain relief

“On the other hand, the study also demonstrated that Bediol® worked just as well as the opioid oxycodone for pain relief in some patients, despite the many dropouts during the study. Although the study design and findings do not allow us to draw conclusions that the side effect profile of Bediol® is better than that of oxycodone, it is clear that the use of opioids is more dangerous than the use of cannabis. Using opioids can cause respiratory depression, which can lead to death. That is not the case with cannabis.”, Kowal says.

Kowal: “In sum, I think that the most important conclusion from this study is that cannabis may be an effective pain treatment for some patients, but that it is certainly not for everyone. It is therefore crucial to determine which factors contribute to a good response to cannabis treatment.”

Medicinal cannabis may potentially reduce pain intensity. This is the conclusion of the Bedrocan research team, which analysed the results of eleven studies in which the cannabis products Bedrocan® and Bediol® were used to treat various pain-related medical conditions. The results of the literature review have been published in the scientific journal Frontiers in Pharmacology in a special issue about the therapeutic potential of cannabinoids under the title ‘The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review’.

In total 18 papers investigated the acute effects of standardised cannabis products in different medical conditions. Eleven of these papers assessed subjective pain as the main outcome measure in pain-related medical conditions such as fibromyalgia, chronic pain, and migraine. Cannabis varieties used in these studies included Bedrocan® (22% THC) and/or Bediol® (6.3% THC; 8% CBD), with large differences in the route, dose and frequency of administration.

Nevertheless, all studies demonstrated a significant reduction in pain intensity. Treatment with medicinal cannabis demonstrated a mild safety profile with feeling high, coughing and mental confusion as the most frequently reported side effects. Other studies reported a relief in symptoms of Alzheimer’s Disease, Post Traumatic Stress Disorder, Tourette’s Syndrome, and Attention Deficit Hyperactivity Disorder.

Side effects and drop-out rates

The review team would like to add a footnote to the results. Although all studies demonstrate a decrease in subjective pain intensity, this evidence mainly comes from observational and retrospective studies. Despite a generally mild safety profile for most patients, some cases of discontinuation of cannabis were also observed. These were primarily due to side effects such as confusion. Two possible factors involved in the experience of side effects and drop-out rates were cannabis use history as well as a higher dose of THC-dominant cannabis. For other medical conditions, it is even harder to draw conclusions because of the limited availability of scientific studies. Future research should focus on conducting randomised clinical trials with sufficient sample size to determine whether patients could benefit from treatment with standardised medicinal cannabis.

Systematic literature review

Bedrocan’s research team identified and included a total of sixty papers that conducted research with standardised cannabis products/varieties from Bedrocan in the systematic literature review. Research topics addressed in these papers could be subdivided into the following four categories:

1. pharmacokinetics of THC and CBD
2. acute subjective experiences
3. impact on cognitive assessments
4. influence of CBD:THC ratios on acute outcome measures.

The current systematic literature review is the first review about the acute effects of standardised cannabis products/varieties from Bedrocan in healthy volunteers and patients. Read the full outcome of the review on the Frontiers website.

Bedrocan is returning to the Canadian medicinal cannabis market. The company purchased a facility in Scarborough, the former home of Bedrocan in Canada, and was recently granted a cultivation license by Health Canada. These steps fulfil Bedrocan’s long-held promise of returning to Canada to grow standardised medicinal cannabis for Canadian patients. The company intends to start production in early 2025.

Benefit patients

Bedrocan is solely focused on producing medicinal cannabis and is known for its high-quality cannabis products with consistent levels of THC and CBD. Bedrocan’s CEO Jaap Erkelens on Bedrocan’s attention to patients: “We have had a strictly pharmaceutical approach since our foundation in 2003. We use the knowledge we have acquired in more than twenty years of business to produce cannabis products that benefit patients exclusively. In the same vein as prescribing physicians, patients want a reliable, standardised product with the same therapeutic effect time after time.”

The intention is for Bedrocan to bring several standardised cannabis products to the Canadian market of which the Bedrocan® product is the most well-known. The products will be distributed through a third party via the medical sales channel to registered patients.

Canopy Growth

Bedrocan was previously active in Canada but ceased its activities after a partnership with Canopy Growth was terminated. Bedrocan has always expressed its intention to return to Canada one day. “We are thrilled to be coming back to Canada,” said Erkelens. “We look forward to serving patients in Canada and positively impacting the Canadian healthcare landscape.”