When it comes to medicines and drugs, one fundamental truth is that everybody is unique. Each individual experience different effects, and reacts differently based on many factors, including biology, life history, mental state, mood, and even transient factors such as how much food or sleep you have had recently. As such, some people may experience anxiety or paranoia when smoking weed, while others find it relaxes and relieves such conditions. In this article, we will try to elucidate why these differences occur and discuss some ways to decrease the possibility of paranoia from cannabis consumption.

The cannabinoids in cannabis, such as THC and CBD, affect receptors in the body’s endocannabinoid system. The central nervous system is highly responsive to triggers of the CB-1 receptors by both endogenous cannabinoids and exogenous ones such as THC. When consuming THC, a wide range of psychoactive effects are experienced depending on the individual and the strain of cannabis ingested. Effects can range from euphoria, bliss, and relaxation to anxiety, paranoia, and depression. For the most part, users report enjoyable experiences, and except in the case of over-consumption, negative experiences are rare.

In those cases where negative emotions are experienced, they are usually short-lived and non-life threatening, however uncomfortable at the time. Often, such negative experiences are put down to set and setting, meaning that the user was already in a negative state of mind due to personal issues or environment, and smoking weed exacerbates these feelings. But more recent studies have looked at the biological effects of cannabis on paranoia, and are beginning to theorize on the mechanisms in which weed can cause paranoia.

The symptoms of overconsumption include anxiety, paranoia, tachycardia, sweating, confusion, disorientation, and nervousness. However, these effects are not life-threatening and tend to subside after a few hours, depending on the route of administration and amount of cannabis consumed. In Emergency Rooms, patients admitted due to an overdose of cannabis are just given medications to treat nausea and anxiety, given a place to relax, monitored, and then released, usually with little to no long-term effects. Other than cases of overconsumption, the long-term use of marijuana is generally well tolerated. There are instances in which long-term cannabis use has been associated with psychosis, however, such cases appear to be treatable. While there seems to be some consensus that cannabis use can reveal latent psychotic disorders, the scientific community is still unable to prove with certainty that a specific type of psychosis associated with cannabis use exists.  

However, since the advent of synthetic cannabinoids the prevalence of paranoia, hallucination s, and other negative psychoactive reactions have been increasingly reported in both scientific studies and calls to poison control centers. Some researchers have put this down to the lack of so called “entourage compounds” present in the cannabis plant, but not in synthetic versions of cannabinoids used in clinical trials. It is theorized, although not proven, that the terpenes and CBD in cannabis help to regulate the high from THC, and when removed, lead to stronger psychoactive effects which can be uncomfortable for users. Several studies using synthetic THC such as Nabilone or Dronabinol have shown pronounced negative psychoactive effects that are not normally associated with the use of whole-plant cannabis.

In areas where weed is illegal, particularly in the UK, synthetic cannabinoids such as ‘Spice’ or ‘K2’ is a growing black market industry. As of 2016, there are around 140 synthetic cannabinoids on the market. These synthetic cannabinoids differ from weed. The THC found naturally in weed is known as a partial agonist of the CB-1 receptors in the body’s endocannabinoid system. Synthetic THC, on the other hand, has been shown to act as a non-selective, full agonist of the same receptors, making the substances between 2-100 times stronger than the natural version and longer-lasting. According to a 2015 review, case reports involving synthetic cannabis overdoses include symptoms such as alterations in mood, perception, tachycardia, seizures, kidney failure, and cardiac arrest. In another review of Emergency Room visits in the US, it was found that 59.3% of patients admitted due to overdose of synthetic THC had serious medical outcomes. A 2016 study concluded that synthetic cannabinoids had “significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana. With the rise of such synthetic cannabinoids, researchers are now beginning to understand the mechanisms through which THC can cause negative psychotic reactions such as anxiety and paranoia in the human brain.

Although many studies have encountered patients experiencing negative psychoactive effects such as paranoia, only one study has thus far focused on this reaction. The 2015 study, published in the Schizophrenia Bulletin, used 121 volunteers with previous histories of paranoia. In the placebo-controlled clinical trial, participants were injected with either pure THC (Dronabinol) or saline and given a self-assessment test to rate their levels of paranoia. The study found that THC “significantly increased levels of paranoia” in the subjects receiving the treatment over the control group. Although brain scans were not used in this study, the author’s hypothesized that the mechanism of action was due to “an anomalous internal state,” including changes in “sensory intensity, distorted sensory experience, sensory flooding, thought echo, and hallucinations.” So, although this study does lay the groundwork for an increased mechanistic understanding of how THC can cause paranoia, it is by no means conclusive and should be reiterated that it used synthetic THC and participants who were already predisposed to such mental states. Further studies using fMRI and other diagnostic techniques are needed to better understand the relationship between THC and anxiety or paranoia.

If you are a first-time weed user and are concerned about the risks of paranoia or anxiety then there are some things you can do to mitigate the risk and increase the likelihood of a pleasant and pleasurable experience. The first would be to relax and stop worrying, the incidence of negative reactions to weed are rare, and worrying about such effects could be a self-fulfilling prophecy. 

We recommend the following tips:

• Start slow. Try smoking or vaping just a little bit and see how you react, if you like it, take more. Avoid edibles or tinctures your first time as it is harder to titrate the dose and the effects are more long-lasting.
• Set and Setting. Try weed when you are in a good mental state, a comfortable and safe setting, and amongst people you are comfortable with. Intentionally designing your first experience to reduce any sources of stress or worry can ensure that it is a pleasant one.
• The Strain Matters. Different strains have different cannabinoid percentages and terpene profiles. As such, each strain will affect you differently. Ask your budtender for a strain with a mellow high and lower THC content. Remember that you want to look at the moods of the strain, not indica or sativa, as the effects associated with those terms are not based on science at all.
• Try a strain high in CBD. CBD primarily affects the CB-2 Receptors in the periphery of the nervous system and is thought to help mitigate the psychoactive effects of THC. It may also reduce anxiety, and improve sleep or relaxation.