Medical Cannabis: Finding the Sweet Spot Between Therapeutic Benefits and Adverse Effects 

I. Introduction

Cannabis has been used for medicinal purposes for centuries and is currently gaining widespread acceptance as a treatment option for various medical conditions. However, determining the optimal dosing and administration of medical cannabis remains a significant challenge. This is due to the complex interplay of the endocannabinoid system, individual differences in endocannabinoid tone, lack of quality-controlled cannabis-based medicinal products, and the variability in dosing for different medical conditions and patient populations. Additionally, the lack of standardized dosing guidelines and the limited availability of quality-controlled medical cannabis products further complicate the issue. There is a need for an updated scientific summary of the current evidence on optimal dosing and administration of medical cannabis to provide guidance for healthcare providers and to improve the safe and effective use of medical cannabis as a treatment option. This article aims to review the challenges associated with determining optimal dosing and administration of medical cannabis and to provide an overview of the current evidence on this topic.

Cannabis has been used for medicinal purposes for centuries, dating back to ancient China and India, where it was used to treat a variety of ailments such as pain, nausea, and inflammation (1). The plant contains over 100 different cannabinoids, with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most studied and commonly used for medical purposes (2). The endocannabinoid system, which consists of endogenous cannabinoids, their receptors, and enzymes involved in their synthesis and degradation, plays a crucial role in regulating various physiological processes, such as pain perception, mood, appetite, and sleep (3). However, determining the optimal dose and administration method of medical cannabis remains a significant challenge. This is due to the complexity of the endocannabinoid system, which can vary widely between individuals due to genetics, lifestyle, medical history (4). Additionally, there is significant variability in dosing for different medical conditions and patient populations, which can make it difficult to develop standardized dosing guidelines (5). Furthermore, the lack of quality-controlled medical cannabis products and the limited availability of standardized dosing methods and guidelines further complicate the issue (6).

II. Background

Medical cannabis has been a topic of growing interest in recent years, with numerous studies demonstrating its potential therapeutic effects in a diverse set of diseases. The endocannabinoid system (ECS) has been identified as a key player in mediating these effects, as it is involved in regulating various physiological processes such as pain perception, mood, appetite, and sleep (3). The ECS is composed of endogenous cannabinoids, their receptors, and enzymes involved in their synthesis and degradation. While delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most studied and commonly used phytocannabinoids for medical purposes, the cannabis plant contains over 100 different phytocannabinoids, each with their own unique profile of potential therapeutic properties (7). Despite the potential benefits of medical cannabis, determining the optimal dosing and administration methods for different medical conditions and patient populations remains a significant challenge. Endocannabinoid tone can vary widely between individuals due to genetics, lifestyle, age and medical history, which further complicates this issue. Additionally, the lack of standardized quality-controlled medical cannabis products and the limited availability of standardized dosing methods have hindered progress in this field (6). However, recent advancements in research and technology hold promise for addressing these challenges and improving the overall understanding and use of medical cannabis.

III. Factors Affecting Optimal Dosing

The optimal dosing of medical cannabis can vary widely between individuals due to several factors. (8) One of the primary factors is the patient’s medical condition, with some conditions requiring higher doses for therapeutic effects than others. (9) The method and route of administration can also impact dosing, with inhalation leading to a much quicker onset and shorter duration of effects, while oral ingestion leads to slower onset and longer duration of effects. (10) The route of administration can also impact bioavailability, with inhalation and sublingual administration having higher bioavailability than oral ingestion. (10) The pharmacokinetics of individual cannabinoids also play a role in determining optimal dosing, with different cannabinoids having different absorption, distribution, metabolism, and elimination profiles (10). Additionally, patient-specific factors such as genetics, age, weight, and medical history can also impact the optimal dosing of medical cannabis. Due to the complexity of these factors, determining the optimal dosing of medical cannabis can be a significant challenge, and standardized dosing guidelines have yet to be established. (9) Furthermore, the lack of quality-controlled medical cannabis products and the limited availability of standardized dosing methods further complicate the issue.

IV. Current Evidence on Optimal Dosing and Administration

Current evidence on optimal dosing and administration of medical cannabis is limited due to the complex interplay between various factors affecting dosing. However, several studies have provided some insights into the optimal dosing and administration of medical cannabis. One study found that lower doses of THC were more effective at reducing pain in patients with chronic pain, while higher doses conversely increased pain sensitivity (11). Another study found that low doses of THC and CBD had a synergistic effect in reducing anxiety, while high doses had an opposite effect (12).

These seemingly contradictory observations are likely due to that the cannabinoids show biphasic properties, meaning that their effects vary depending on the dose administered. This phenomenon has been observed with many bioactive phytocannabinoids, including THC, CBD, CBG, CBN and THCV (13,14). Therefore, it is essential to consider the biphasic properties of cannabinoids when determining the optimal dosing and administration of medical cannabis. This is the main reason why physicians should always advise their patients starting with medical cannabis to begin with a slow dose-escalation during the first two weeks of treatment.

Overall, while current evidence is limited, these studies suggest that the optimal dosing and administration of medical cannabis may depend on the patient’s specific medical condition, the method and route of administration, and the individual’s response to different doses of cannabinoids. Further research is needed to establish standardized dosing guidelines and to better understand the complex pharmacological properties of cannabinoids (14).

V. Guidelines for Healthcare Providers

Given the complexity of factors influencing optimal dosing and administration of medical cannabis, healthcare providers need to exercise caution when prescribing it to patients. Here are some guidelines that can help healthcare providers to effectively prescribe medical cannabis:

• Conduct a thorough patient assessment to determine the medical condition, previous medical history, and current medications.
• Consider the patient’s age, gender, and body weight in determining the dosage and administration method.
• Always start with a low dose and gradually titrate up until the desired therapeutic effect is achieved.
• Consider the method of administration, with inhalation leading to a quicker onset of effects but shorter duration, and oral ingestion leading to slower onset but longer duration of effects (10).
• Be aware that the risk for potential adverse effects, such as dizziness, dry mouth, somnolence and cognitive impairment, increases as THC doses rise (15).
• Educate patients on the potential risks and benefits of medical cannabis, and ensure they understand the importance of following dosing instructions and not sharing their medication with others.
• Monitor patients closely for signs of tolerance or dependence and consider lowering the dose or tapering off the medication if the patient experiences more adverse effects than therapeutic benefits (16).

While guidelines for medical cannabis use are still being developed, healthcare providers can use the available evidence to make informed decisions about dosing and methods of administration. Close monitoring and ongoing communication with patients can help ensure the best outcomes. In conclusion, medical cannabis can be a valuable treatment option for patients with a range of medical conditions, but healthcare providers must exercise caution when prescribing it. Thorough patient assessments, consideration of patient characteristics, and gradual dose titration can help ensure the best therapeutic outcomes while minimizing potential adverse effects.

VI. Conclusion

In conclusion, the optimal dosing and administration of medical cannabis is complex and multifactorial. The individual patient’s medical condition, age group, gender, route of administration, formulation of the drug, and the pharmacokinetics of individual cannabinoids all play a role in determining the optimal dosage. Additionally, the biphasic properties of cannabinoids and the potential for receptor downregulation with chronic use further complicate optimal dosing (10,17,18). Standardized dosing guidelines have yet to be established, and further research is needed to identify effective dosing strategies for specific medical conditions (19). Healthcare providers should take a patient-centered approach and closely monitor patients for adverse effects and therapeutic efficacy. It is recommended to start with low doses and titrate up gradually as needed while also considering potential drug interactions and individual patient response (20). In addition, patient education on the potential risks and benefits of medical cannabis is essential for informed decision-making and adherence to treatment plans. Overall, medical cannabis has shown promising therapeutic effects, but more research is needed to fully understand its optimal dosing and administration for specific medical conditions. For now, the best guidelines remain start low and go slow.

Stefan Broselid, Ph.D.
Molecular Pharmacology
Editor-In-Chief, Aurea Care Medical Science Journal

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