by Seshata on 22/01/2016 | Consumption

The complex effects of nicotine when mixed with cannabis

Nicotine Tobacco and cannabis have a strange relationship, one that has lasted for centuries but has been continually turbulent. Why do so many people use the two together? As usual with cannabinoid science, the truth is stranger than anything that could be dreamed up.

Tobacco and cannabis are very often consumed together

The two substances have been consumed together for centuries by people throughout the world, in Europe, Africa and Asia. In fact, it is thought that up to 70% of people that use cannabis also use tobacco. Even in North America, where cannabis is traditionally smoked pure, many users also use tobacco.

Tobacco has been mixed with cannabis for centuries, throughout the world (© Wikimedia Commons)
Tobacco has been mixed with cannabis for centuries, throughout the world (© Wikimedia Commons)

Furthermore, there are many users in North America who smoke cigarettes immediately after smoking cannabis, who are likely to experience similar synergistic effects to those that actually mix the two together (indeed, many do so for the perceived experience of getting “more high” as a result).

Differences in effect are widely reported

Many users report subjective differences between the effects of cannabis alone and cannabis when mixed with tobacco.

The most common reported effect of smoking tobacco alongside tobacco is an intensification of the “high”, although some report that tobacco use actually has the opposite effect and reduces the high. Another commonly reported effect is to “calm” the user down from the sometimes anxiety-inducing effects of cannabis.

The biological mechanisms underlying this strange relationship are wildly complex, and are linked to various other processes now known to be related but long believed to be essentially separate. Indeed, the more we learn about these interlinked systems of reward, craving, addiction, and satiety, the more we begin to understand that every aspect of our brains and bodies is inseparably intertwined.

Cannabis, tobacco and the hippocampus

A widely-reported recent study correlated cannabis use with reduced volume and density of the hippocampus, an area of the brain that is associated with memory, inhibition and addiction. This was also demonstrated in this study from 2011, although the effect here was found to depend on various factors including ratio of THC to CBD. At least one other study has found no long-term change, and one study highlighted the possibility that genetic differences may alter the hippocampal response to cannabis use.

This reduction in size was found both in cannabis-only users and in cannabis/tobacco users, and was not found in nicotine-only users. In cannabis-only users, the small hippocampus was found to correlate with poor memory (this is unsurprising, as good hippocampal health and size usually correlates positively with good memory). So, within the group, the smaller the hippocampus, the poorer the memory.

The hippocampus is an area of the brain that somewhat resembles a seahorse, and is the HQ of the interlinked processes of stimulus, reward and addiction (© Wikimedia Commons)

However, the researchers also found something very surprising indeed: in the cannabis/tobacco-using group the reverse was true, and smaller hippocampal volume correlated with improved memory! Subjects that smoked higher numbers of cigarettes exhibited greater decreases in hippocampal volume, and relatively higher memory scores (although memory was still generally poorer than in all other groups).

While this study was limited in scope and design, and establishes correlation but not causation (as a cross-sectional study looking at a brief window of time, it is inferior to a longitudinal study, for instance, which would follow subjects for extended time periods to better track changes and establish causation), it still demonstrates an unusual effect, and one that has yet not been fully explained.

How all the main regulatory and signalling systems are linked

It now appears that tobacco, cannabis, and other psychoactive substances such as opioids are all linked together in a complex network of stimulus and reward, with the hippocampus essentially functioning as the HQ for operations.

Throughout the body, and particularly in the brain, we have cannabinoid receptors (as our readers will no doubt be aware!), as well as opioid and nicotinic receptors. Within the brain, densities of these receptors are extremely high in the hippocampus, and are also very high in the amygdala (both areas are heavily associated with stimulus, reward, addiction and so on).

The agonists (activators) of these three types of receptors (of which the best known are THC for the cannabinoid receptors, nicotine for the nicotinic receptors, and morphine for the opioid receptors) are hugely important in terms of the psychoactive and physiological effects they can exert. In fact, even substances that inactivate the receptors (like CBD for the cannabinoid receptors and naxolone for the opioid receptors) are of great interest due to their opposite effects.

How deeply are these systems interlinked?

While we’ve known about these systems for years, we are only recently beginning to understand the extent and depth of the connections that they have with each other. Indeed, it’s pretty difficult to really see them as separate systems at all, given the innumerable, criss-crossing links that flow back and forth between them.

Here’s a brief look at how these systems can affect each other. We know that nicotine itself acts on the opioid (and possibly cannabinoid) receptors as well as the nicotinic receptors themselves. We also now know that prolonged exposure to nicotine apparently reduces the number of CB₁-receptors in the hippocampus.

The brain’s response to nicotine, alcohol, cannabis and other habit-forming substances is complex, and not fully explained (© Brian James)

We now also know that substances that block the CB₁-receptors can cause people and animals to stop craving both nicotine and morphine. Thus, agonists of the CB₁-receptors may cause increased cravings for nicotine, which may explain the common desire to smoke cigarettes immediately after cannabis, or the heightened subjective level of satisfaction derived from smoking the two together.

In fact, it seems that to get any “rewarding” effect at all from using sugar, nicotine, alcohol or cocaine, we need to activate the cannabinoid receptors; no activation, no release of dopamine, and no subject experience of pleasure!

There also appears to be a genetic element to all this—variations in the CNR1 gene (which encodes for the expression of CB₁-receptors) are associated with variations in susceptibility to nicotine dependence. This association is found in white females and not white males (whites were the only race tested in the study).

So what does all this mean?

Well, we’re still a long way from developing a precise understanding of all the different processes that occur in the brain in response to the introduction of psychoactive substances, alone or in combination.

But we are now beginning to come to terms with this vast complexity, and to realise that investigation of any substance use or abuse or any psychiatric illness cannot be done in a vacuum—for example, we can no longer point the finger at cannabis and blame incidences of psychosis solely on its use, now that we are aware of exactly how much influence other factors such as nicotine use may play.

Now that we are able to view this vast and interconnected system for what it is, we are also giving ourselves increased ability to make nuanced judgements on individual cases, based on a much wider and more cohesive set of factors, influences and interrelationships.

So how do we put this knowledge into practice?

The interactions between nicotine and THC are complex and heavily dose dependent, and are no doubt dependent on a host of other variables that science is either unaware of or is just beginning to grasp.

Research has even shown that blocking the cannabinoid receptors causes craving for opiates and nicotine to cease! (© JoshNV)

Tobacco use has often been overlooked when investigating the cognitive and psychiatric effects of cannabis, despite the established knowledge that nicotine is a psychoactive substance in its own right. This oversight seems even more egregious when considering the extremely high incidence of cigarette smoking among sufferers of certain psychiatric conditions, including schizophrenia.

Indeed, recent research is finally beginning to tackle this subject head on, and has somewhat unsurprisingly found that nicotine is strongly associated with development of psychosis! The author of this recent study, James McCabe of King’s College London, is on record as stating “it might even be possible that the real villain is tobacco, not cannabis”.

Nicotine is generally negative for health and should be avoided. However, studying the differences between users of nicotine and cannabis alone compared to users of both has given us some important insights into the interconnected nature of the brain’s signalling and reward systems.

From this and other relevant research, we now know that the EC system is heavily involved in the regulation of stimulus and reward, and has a huge part to play in addiction to substances such as nicotine and morphine.

Comment Section

Post a comment

Daniel Williams

Very nicely done – thanks.


James Kratz

Awesome piece! Can’t wait for more research!


chic zucco

anyone who mixes pot with tobacco is stupid,it tastes nasty and cigarettes are nasty to begin with,so shove that tobacco up your asses,got it?



Let me guess, you vape?

Rude. Go waste your worthless opinion at a Trump rally or something, they seem to be more your crowd.


James Bond

That was the most scientifically detailed article followed by the most blunt and unintelligent response. So interesting who you find on the web. I would be surprised if CHIC knows how to read past the first sentence.

Great article and thanks for the references!



Nicotine gum, get all the nicotine without the harsh flavor and the chance for cancer.



Great article!



Thank you for addressing this important issue. Reward-hunters find cannabis helps them enjoy their feel-good, reward-for-its-own-sake drug, then cannabis blamed for the results.

Ironically some editor obeyed a kind of convention to post a picture of how to combine cannabis with nicotine in a Joint, maybe because it seemed correct and pertinent, meanwhile the picture made Seshata’s entire article seem to endorse the drug-admixture rather than criticize it.

What if Mom is reading this article and a 2-year-old or 5-year-old sees that picture– will they think Mom is reading an article which shows how to make a $igarette? “For children whose parents followed the longtime social rules to keep them ignorant about cannabis, every Joint and every picture of a Joint is a $igarette advertisement.” Re mixture, an Australian Department of Health advisory suggested that the tobacco-infested Joint was a Trojan Horse designed to lure children experimenting with cannabis into nicotine $igarette addiction.

Remedy: mixture with tobacco can be avoided by SUBSTITUTING a 25-mg Single Vapetoke Utensil (flexdrawtube one-hitter) for the hot burning overdose monoxide 700-mg $igarette or 500-mg Joint. (Requires 1/16th inch pre-sifted herb.) Eventually users may achieve SUBSTITUTION of cannabis– and alfalfa, basil, chamomile, catnip, damiana, eucalyptus etc.– for tobacco.



In traditional Indian recipe of ganja, it is to be mixed with 10% tobacco (there are other ingredients also added but I won’t go into that). The effect of the small amount of tobacco is that its stops one becoming to slow from the ganja. If to much tobacco is added it can have negative effect on blood pressure.



Thanks for this valuable information. Could you go further in detailing the traditional Indian recipe?



I use tobacco in my joints to help them burn. I've never smoked a pure bud joint without it having to be relit every couple of tokes. If that didn't happen, I wouldn't use baccy.



Mother earth stops burning herself so you can relight and put more in your body.



Its all down to how you roll them,a pure cannabis joint will not really go out while smoking it if you get the tensisity and fineness of cannabis, well ground right.I never really have that problem now as ive learnt the right way to make it work. If not smoked fairly quickly however,but not rushed at all, it will always go out faster than one with tabacco but this is never really a problem if done correctly, and often an advantage as smoking it pure you often are going to be saving some if smoking alone. Re the combination of tabacco and cannabis i find its just basically a different high or whatever you like to call it, a different effect,the effect of the cannabis seems to me to be just not as good or intense so you do not get all the benefits from it, ie the relaxation etc, but it seems to create a more foggy "stoned" effect where you feel like youre more stoned but its the mixture as cannabis alone doesnt have that effect on me. Im so happy i gave up tabacco, its highly addictive, cannabis is not, its also highly unhealthy and seems to elude the point of smoking cannabis at all!!!! Its not a good combination, especially now with all the chemical packed cigarettes ppl buy, they are far removed from what pure tabacco, properly cured and dried should be like, so if you like that part, invest in a tub of something without all the chemicals and give yourself and ppl around you a break form the pollution.


David Hollosi

I am not heavy user but i need something to stay on the path.I am having 2-3 joints weekly strictly weekends only and i am adding tobacco because its too harsh for me without it.Not a big load just a bit but i am non smoker and i dont drink alcohol so im not worry too much.
Great research though.



Learn some appreciation, if you aint hooked on tobacco dont use it



ya'll should get a tobacco replacement.
best one I know is real leaf



I was sad to learn that THC may decrease size and density of hippothalamus (memory center). I've noticed the effects as I forget things much easier now that I've started dating Maria again :/



i did 3 times, you are wasting my time



In the article it is said (beneath one picture): "Research has even shown that blocking the cannabinoid receptors causes craving for opiates and nicotine to cease! "

Be careful here!! Research cited considered the use of "rimonabant". The author neglects to cite later research (2008 ff) warning for the use of "rimonabant" because of its serious side-effects (depression, anxiety). This drug has not been approved in many countries (incl. USA).

James R. Grit


Scarlet Palmer

Hi James,

Thank you for your comment and for bringing this important point to my attention. I will get in touch with the author of this article and amend it as needed. In the meantime, I hope you continue to enjoy the blog.

With best wishes,




Great article. Wonder if the results would be similar mixing blue moon CBD vape juice and e-nicotine, or if the THC is also a key component in the outcome of the mix.


Leave a Comment

Please enter a name
Oops, looks like you forgot something?
Read More
Read More