CBD:THC Ratios and How it Effects the Human Body

What ratio is the most effective?

Posted June 30, 2020

General guidelines and clinical relevance of medicinal cannabis with both CBD and THC

This article specifically comments on the dosing of each and the necessary ratios of CBD:THC for meaningful clinical effects.

Cannabis has been known for centuries, not only for its psychoactive effects but also for the plant’s medicinal properties for pain relief, appetite stimulation, and anxiety reduction. Those properties are mediated by the various phytocompounds in the cannabis plant, most specifically tetrahydrocannabinol (THC) and cannabidiol (CBD). While there are over 100 phytocannabinoids in the cannabis plant, CBD and THC are the two primary ones discussed in scientific literature. As it turns out, these two primary phytocannabinoids have completely different effects on the human body. However, they can also potentiate or antagonize each other depending on the ratio they are administered with and the time in between their administrations. In this article, you will learn about the interactions between CBD and THC and their effects on the human body.

Interactions of CBD and THC in the Endocannabinoid System

The endogenous cannabinoid system (ECS) consists of CB (cannabinoid) receptors, endocannabinoids (compounds that interact with the receptors), and the enzymes that break them down. This is a biological system first written about in 1992 and its main role seems to be related to the regulation of the neurotransmitters inside the brain, but the system is far-reaching and also modulates inflammatory regulation and more.

Currently, we know that two types of receptors exist: CB-1 receptors can be found mainly in the brain and CB-2 receptors can be found mainly in immune cells (but also in the brain and other organs). (1)

Endocannabinoids, the ones naturally synthesized by the body, are normally broken down quite rapidly by various enzymes. Their role is to affect only a short-term signal and influence local changes to regulate the release of other neurotransmitters. There are many different endocannabinoids but the most well-known are anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

THC and CBD are both responsible for various pharmacological effects inside the body by interacting with the CB receptors. THC triggers the CB-1 receptors inside the brain which primarily leads to the psychoactive effects. However, it is not rapidly broken down like AEA and other endocannabinoids, therefore its effects can be long-lasting, relatively speaking. Additionally, the effect of THC is not local or limited. THC effects all CB receptors inside the brain at the same time. (2)

On the other hand, CBD doesn’t bind as strongly to CB receptors as THC. CBD affects mostly CB-2 receptors and doesn’t have any psychoactive effects. Instead, it might possess anti-inflammatory properties. CBD is also an agonist for the serotonin 1A receptors. (3) This is why it has antipsychotic and anxiolytic effects.

CBD Protects Against the Adverse Effects of THC

THC is not a totally benign substance. While many people can use it repeatedly without adverse effects, THC can increase the risk of psychosis in sensitive individuals.

A 2009 study collected data from 454 regular cannabis users; 280 with psychosis and 174 healthy controls. 78% of the group with psychosis regularly used high-THC cannabis compared to 37% of the control group. (4) The study elucidated the fact that the subjects with psychosis were more likely to be daily high-THC smokers and they had smoked THC-containing cannabis for more than five years.

Studies in mice have also found out that THC can lead to problems with short-term memory. According to the research, this is mediated by the specific effect of THC on the CB-1 receptors. (5) Furthermore, THC can trigger symptoms of anxiety in sensitive individuals. A study with 23 healthy cannabis users investigated the effects of placebo, high THC or low THC marijuana on their anxiety levels. Compared to placebo, THC increased overall symptoms of anxiety and the response was higher with increasing the THC content. (6)

Interestingly, marijuana with higher CBD content reduces some of the negative impacts of THC on the brain such as increased anxiety and psychoactive effects. This is confirmed by multiple studies as well as double-blind trials. Even studies performed back in the 1980s, ten years before the discovery of the ECS, showed that CBD can antagonize the effects of THC. (7) Now we know

that these THC mitigation effects might be due to CBD inhibiting the enzymes that break down the endocannabinoid AEA. This prolongs the effect of AEA which preoccupies the receptors, inhibiting THC from binding to them. This is the primary way we know of in regard to CBD’s antagonistic effects against THC when both are taken simultaneously. (8) Furthermore, CBD might protect against possible neurotoxic effects of excessive THC thanks to its effects on intracellular calcium levels. (9)

Effects of Different CBD/THC Ratios for Various Conditions

While we have clear evidence that CBD modulates the effects of THC, it is difficult to establish the exact CBD/THC ratios that could lead to stronger or weaker antagonism. This is because other factors could interfere with these cannabinoids' ultimate effects, such as the time in between administration of the two.

Studies in rats have shown that ratios of CBD/THC of 20:1 significantly reduced the effects of THC. However, CBD/THC 5:1 or lower, especially if CBD is administered 20 minutes beforehand, can possibly potentiate the effects of THC. (10) It is unclear if a similar potentiating effect is possible in humans.

For cancer patients, it might be best to use a combination of CBD and THC. While THC is approved by the FDA for treating nausea and vomiting associated with cancer chemotherapy for non-responders, studies suggest that the addition of CBD also reduces cancer-related pain. A double-blind, placebo-controlled trial reported that low dose CBD/THC combination in 1:1 ratio (2.5 mg each) significantly reduced pain. THC alone was not found to be significantly more effective than a placebo. (11)

Another study investigated the effect of CBD/THC in a ratio of 20:1 for at least 3 months on 46 patients with refractory epilepsy. The average CBD dose was quite high - 11.4 mg/kg/day. Twenty-six patients had ~50% reduction in monthly seizure frequency and higher doses were associated with even better management of the symptoms. (12)

A high CBD/THC ratio might also have good application for treating various addictions including cannabis dependence. A study reported that smokers of high CBD/THC show reduced attentional bias to drug and food stimuli compared with smokers of low CBD/THC. (13)

The Food and Drug Administration (FDA) has approved low-dose THC for treating nausea and vomiting associated with cancer chemotherapy for non-responders, and for treating AIDS-associated weight loss. The initial oral dose recommended is 0.04 mg/kg given twice per day.

A prescription CBD drug product is approved by the FDA to treat rare, severe forms of epilepsy with an initial oral dose of 2.5 mg/kg, twice per day.

The Take-Home Message

The research on the optimal ratio between CBD and THC is still ongoing. We need more studies investigating all other factors which can also interfere with their combined effect on the body to comment substantially on the topic.

However, the studies so far clearly show that both CBD and THC can modulate various processes in the brain as well as influence human physiology as a whole. Despite the potential risks associated THC usage, the addition of CBD seems to have a protective effect against excessive activity of cannabis’s psychoactive compound.

The endocannabinoid system is far-reaching within the human body which is why phytocannabinoids have promising therapeutic potential extending far beyond the common psychoactive effects of cannabis.

References: