Demystifying the Varied Reactions to Cannabis Consumption

Cannabis has different effects for different people. While there is ample information about specific strains and psychoactive effects online, they are a general guide at best. You cannot predict how a strain will impact you until you have tried it.

Some Indica strains are more likely to sedate you, for example. Other strains are notorious for appetite stimulation and a sometimes uncontrollable (but pleasant) case of the munchies. Specific strains of cannabis can be effective at lifting your mood and creating a sense of calm relaxation for people with anxiety disorders.

One of the things that has confounded researchers is how two people can consume the same cannabis products and experience different psychoactive effects. One person may experience higher levels of impairment than the other as well.

Let’s dive into some of the reasons why people can react differently to the same cannabis strain, product, and potency.

Why Do Some People Get More High?

Have you ever noticed that some people get more impaired by cannabis than others? You can be smoking the same strain, feel fine, and look over to see a friend who is quickly settling in for a couch crash. While they are sleeping it off, you may have wondered why you didn’t experience the same effects or level of impairment.

Other psychoactive effects can vary as well. Certain strains of cannabis have a high potential to make you feel euphoric and happy. Stress? What stress! You can thank your favorite strain for turning your frown upside down. But someone else may not have the same uplifting experience; it could heighten anxiety for others, cause paranoia, and, in some cases, symptoms of depressed mood.

Because cannabis can be a wildcard when it comes to physical or psychoactive effects, you may find a few strains that have proven to work well for you. Sticking to known strains is common among patients who use medical cannabis; no one likes unexpected and potentially unpleasant surprises.

Medical researchers know more today than ever before about the variable physical and emotional responses to cannabis. Here are some of the reasons why results vary when people ingest those things called cannabinoids and the many chemical compounds found in cannabis products.

1. Tolerance to Cannabinoids

Let’s start with the most prominent and practical reason why some people get higher (on the same strain) than others. Your tolerance levels determine how your body, and particularly your brain, reacts to cannabis.

Individuals who use cannabis regularly (such as patients) will start to build a tolerance to cannabinoids over time. Just as tobacco smokers ‘level up’ over the years in terms of how many cigarettes they smoke every day, people who use cannabis experience the same process. The same is true for people who habitually consume alcohol.

Eventually, the quantity you are taking (and potency) will stop providing the same effects. For example, after years of using your favorite strain (for chronic pain), you may find that the level of relief isn’t the same. Naturally, you will consider increasing either the quantity or potency of the cannabis you consume to help manage your symptoms.

Marijuana doctors suggest that patients start with the lowest effective dose. It may seem counterintuitive to patients, particularly if they suffer from moderate to severe symptoms. You just want to feel better. However, that recommendation is to help prevent patients from rapidly developing a tolerance to cannabis.

Monitor Your Cannabis Tolerance Levels

Many patients explore medical cannabis because other methods (including prescription medications) have become less effective. Or patients have experienced debilitating side effects as a result of prescription drugs. It can be very effective for many patients and help address symptoms and provide relief.

However, patients who routinely use higher than average potency levels (over 15%) can quickly develop a tolerance to cannabis. The more you take, the more that tolerance increases and that is bad news if you are not able to taper it back and find that cannabis no longer works to provide the symptom relief you rely on.

If you are experiencing problems with cannabis tolerance, you can take a break and reduce your consumption and the potency of medical cannabis products you use. Many people can ‘reset’ their tolerance levels in under six months. Talk to your DocMJ cannabis healthcare provider for guidance on monitoring and adjusting your tolerance to cannabis.

Desensitization of Cannabinoid Receptors

Why does tolerance happen? There are other substances you take daily, like food or water, and you do not develop an increasing tolerance to them, right? It all concerns your cannabinoid receptors, which are CB1 and CB2.

The human brain has the highest quantity of CB1 receptors. The endocannabinoid system is a complex neural network of messages running from the brain and the central nervous system. When you ingest cannabis (by any intake method), the cannabinoids bind with those receptors, creating the physical and psychoactive effects we experience from cannabis.

However, excessive intake of marijuana (called cannabis use disorder) can cause desensitization of the cannabinoid receptors. When that happens, your tolerance to cannabis increases. The exact amount of THC will no longer provide the desired effects you want from medical cannabis.

Upregulation and Induction of Enzymes

There are enzymes in your body that help to metabolize cannabinoids. When you consume cannabis, these enzymes (such as cytochrome P450) start to break down the cannabinoids so they can be absorbed into the bloodstream. Then, the magic of the psychoactive and physical effects of cannabis begins.

When you consume a lot of cannabis over a period of time, notably higher potency products, the enzymes can be upregulated. In simple terms, the human body feels like there are too many cannabinoids to process, which triggers the enzymes into overdrive.

The result after enzymatic activity increases? Tetrahydrocannabinol (THC) is cleared from your body in record time. The enzymes basically flush out the THC faster, and higher levels of potency or quantities of cannabis are required to achieve the same psychoactive effects.

Neuroadaptive Changes in the Brain

Long-term use of cannabis, or chronic exposure to cannabinoids, causes neuradaptive changes in the human brain. What that means is that the brain starts to respond to regular exposure to cannabis in some interesting ways.

The brain adjusts to the influx of cannabinoids by adjusting neurotransmitter release, signaling pathways, and the number of receptors responding to cannabis. That results in reduced sensitivity to cannabis and increased tolerance to cannabinoids.

Cannabinoid Cross-Tolerance

The two major cannabinoids present in medical marijuana are tetrahydrocannabinol (THC) and cannabidiol (CBD). But did you know that there are hundreds of minor cannabinoids? Long-term regular use of cannabis can also cause your brain and body to develop a resistance to the effects of minor cannabinoids.

Behavioral Tolerance to Cannabis

How do you behave when you are high? People who have used cannabis for a long time manage to function better when under the influence of cannabinoids. Some can even appear completely sober, making it difficult to determine if they are impaired at all.

Regular cannabis users develop a behavioral tolerance to cannabis. They know how their body and brain react when they are impaired and have mastered the ability to remain functional when they are high. An essential skill, if you don’t want everyone to know you just smoked marijuana.

2. Delivery Method

The type of intake or delivery method you choose has a significant impact on your impairment level. Some cannabis products have a rapid onset of psychoactive and physical effects, while others can take almost two hours before you start to feel anything at all.

The intake method also determines how long you remain impaired. The intoxicating effects of cannabis can be long in duration or relatively short-lived. There may be times when you want the enduring effects of cannabis, such as during the evening when you want to get uninterrupted sleep.

Smokable Cannabis

• Onset of effects within 3-5 minutes on average.
• Short duration (2-4 hours).
• Inhaled cannabis rapidly enters the bloodstream through the lungs and reaches peak levels of impairment quickly, tapering off within a few hours. The fastest and most immediate impairment from cannabis is caused by smokable flower or vaping.

Cannabis Edibles

• The onset of effects is delayed, taking an average of 1-2 hours before full effects are experienced.
• Cannabis edibles have the longest duration of psychoactive effects, lasting anywhere from 4-7 hours for most people. It is longer if consumed on an empty stomach.
• Edibles take longer to process through the digestive system before the cannabinoids enter the bloodstream. One common mistake people make when using edibles for the first time is misunderstanding the delayed effect. That can lead to overconsumption. Remember to always wait at least ninety (90) minutes before consuming more cannabis after you have taken an edible.

Tinctures and Sprays

Sublingual uptake is the absorption of cannabis through oral doses. Tinctures are dispensed under the tongue and held for at least one minute before swallowing. Because the veins of the underside of the tongue are so close to the surface, they rapidly absorb liquid cannabis. Sprays work the same way.

• The onset of effects can take 15 minutes to an hour.
• Average duration (2-4 hours).
• Effects are more gradual or mild, with a less intense level of psychoactive effects compared to smokable cannabis or edibles.

Cannabis Topical Creams and Ointments

Cannabis creams and topicals provide localized relief but not impairment. You may notice you feel calmer or relaxed, but topicals are the least strong of all intake methods. That is because the cannabinoids penetrate through layers of skin, but almost no cannabinoids enter the bloodstream when you use topicals.

Clinical Inhalers

Similar to asthma inhalers, cannabis inhalation causes a rapid onset of psychoactive effects. Any inhalable cannabis product passes quickly through the lungs and into the bloodstream. The metered dose of cannabinoids from a clinical inhaler can be felt in 3-5 minutes on average and lasts 2-4 hours in duration.

3. Metabolism

Do you have a fast or slow metabolism? Your metabolic rate is very important because it determines how quickly your body absorbs nutrients you consume and (you guessed it) cannabinoids. But, there are a few different aspects of metabolism that contribute to the degree of impairment you experience from cannabis.

Cannabis Absorption Rate

This is a significant factor that determines how high you get after consuming cannabis. Eventually, all intake methods result in cannabinoids entering the bloodstream and being delivered to all body areas.

People with high metabolisms absorb cannabinoids more quickly than those with a lower metabolic absorption rate. Typically, older people have slower metabolisms, which also influences how impaired you become after consuming cannabis.

Liver Metabolism

When THC is delivered to your liver, it is converted to a metabolite called 11-hydroxy-THC. Enzymes jump in (especially the cytochrome P450 3A4 enzyme) to break down THC so it can be delivered to cells in the body.

Low levels of enzymes mean a slower onset of the psychoactive effects of cannabis. Some prescription medications can also inhibit or induce enzyme activity. This affects not only the level of impairment experienced from cannabis but also how quickly THC leaves your body.

4. Neurochemistry

Unsurprisingly, your brain has a lot to do with creating the psychoactive effects that help provide relief, relaxation, and euphoric feelings you experience after using cannabis. Your brain on cannabis may look (and act) very different compared to someone else. It comes down to neurochemistry.

Cannabinoid Receptor Density and Distribution

Individuals can have more or less cannabinoid receptors, depending on the makeup of their brain. It is no surprise that people with a higher density of cannabinoids get more impaired. Where the most dense concentration of CB1 receptors in your brain are located also plays a role.

Sensitivity of the Endocannabinoids System (ECS)

Having a sensitive endocannabinoid system is a good thing. Having one that is less sensitive puts a throttle on the psychoactive and physical effects you would experience from cannabis. If your ECS is sensitive and responsive, efficient neural signaling means you will experience a higher degree of cannabis impairment.

Neurotransmitter levels and a good balance improve the modulations of gamma-aminobutyric acid (GABA), dopamine, glutamate, and serotonin. If they are working at an optimal level, your body will experience more intense psychoactive effects.

Tetrahydrocannabinol (THC) triggers the release of dopamine, or the “feel good” hormone, in the human body. People with lower natural dopamine production will not feel the effects of cannabis as strongly as someone who produces a normal level of the pleasure hormone.

Psychological and Mental Health Factors

Have you ever felt depressed or experienced high anxiety, then consumed cannabis? Many patients have, but sometimes cannabis does not provide the results you were hoping for. You may be sitting on your couch and realize that you still feel stressed, anxious, or sad, even after consuming medical marijuana.

Mental health conditions like depression, anxiety, and more can interact and sometimes block some of the neurochemical effects of cannabis. Researchers are not sure if that is because of the nature of the mental health condition or if that resistance to the psychoactive impacts is related to prescription medications used for anxiety.

6. Health Conditions

If you have certain health conditions, it may actually increase the intensity of your psychoactive experience after using cannabis. There are many physical and mental health conditions that can increase the risk of experiencing an uncomfortably heightened level of impairment.

Psychiatric disorders like schizophrenia, moderate to severe anxiety, and bipolar disorder may amplify the psychotropic effects of cannabis. Some types of mental health conditions are contraindicated or not recommended for medical cannabis use because cannabis can make symptoms worse.

Patients struggling with substance use disorder should talk to a doctor before trying medical cannabis. If you have a history of alcoholism or drug abuse, you may be more prone to experiencing high tolerance levels but also excessive impairment.

7. Genetic Factors

Your genetic makeup also plays a part in determining how impaired you get after consuming cannabis. That includes factors like cannabinoid receptor sensitivity, enzyme levels (P450 2C9 and cytochrome P450 2A4), and the overall functioning of your endocannabinoid system.

If you get very impaired from cannabis, there can be genetic factors causing it. Consequently, if you struggle to experience the psychoactive effects of medical marijuana, it could be hereditary. Not that your parents or grandparents will confirm or deny cannabinoids produce psychoactive effects for them or how intensely they have experienced them.

Joseph Rosado

Dr. Rosado is a passionate educator about alternative medicine and has cared for patients for over forty years after receiving his M.B.A. at the University of Phoenix. Joseph Rosado, M.D., M.B.A. is also the author of “Hope and Healing: The Case for Cannabis.” Dr. Rosado is a Certifying Physician for DocMJ.