Cannabis / Marijuana News

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)
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 CB?-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)
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 CB?-receptors can cause people and animals to stop craving both nicotine and morphine. Thus, agonists of the CB?-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 CB?-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)
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.

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