smoking a cigarette after weed

What Are the Effects of Mixing Nicotine and Cannabis?

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 have been consumed together for centuries by people all over the world. 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.

In fact, it is common in North America to smoke cigarettes immediately after smoking cannabis. This is likely to produce similar synergistic effects to actually mixing the two together (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 cannabis 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 behind this strange relationship are wildly complex. They are linked to various other processes now known to be related, but long believed to be essentially separate. 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 long-term heavy 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. More specifically, higher THC and lower CBD was associated with a volume reduction in the right hippocampus. This indicates neurotoxic effects of THC and neuroprotective effects of 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. It was not found in nicotine-only users, though.

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 in children, adolescents and young adults. So within the group, the smaller the hippocampus, the poorer the memory.

However, the researchers also found something very surprising: 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, establishing correlation but not causation, it still demonstrates an unusual effect, and one that has yet not been fully explained. It is important to note that as a cross-sectional study looking at a brief window of time, it is inferior to a longitudinal study. One which would follow subjects for extended time periods to better track changes and establish causation.

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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 (which are part of the endocannabinoid system) 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 beginning to understand the extent and depth of the connections that they have with each other. It is difficult to really see them as separate systems at all, given the innumerable, criss-crossing links that flow back and forth between them.

Here is 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 subchronic exposure to nicotine increase the numbers of CB1 receptor in the hippocampus and decrease in striatal cannabinoid CB1 receptors.

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 but 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.

We can now view this vast and interconnected system for what it is and we can make nuanced judgements on individual cases, based on a much wider and more cohesive set of factors, influences and interrelationships.

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So how do we put this knowledge into practice?

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

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 endocannabinoid 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.

Some say cigarettes boost your high, others say nicotine ruins your high. Here is what the limited research says on mixing cannabis and nicotine.

Nicotine changes marijuana’s effect on the brain

How scientists study the effects of marijuana on the brain is changing. Until recently marijuana research largely excluded tobacco users from its participant pool, but scientists at the Center for BrainHealth at The University of Texas at Dallas have found reason to abandon this practice, uncovering significant differences in the brains of individuals who use both tobacco and marijuana and the brains of those who only use marijuana.

In a study that appears online in the journal Behavioural Brain Research, scientists report an association between smaller hippocampal brain volume and marijuana use. Although the size of the hippocampus, an area of the brain associated with memory and learning, is significantly smaller in both the marijuana group and marijuana plus tobacco group compared to non-using controls and individuals who use tobacco exclusively, the relationship to memory performance is unique.

Hippocampal size of nonusers reflects a direct relationship to memory function; the smaller the hippocampus, the poorer the memory function. Individuals who use marijuana and tobacco show an inverse relationship, i.e., the smaller the hippocampus size, the greater memory the function. Furthermore the number of nicotine cigarettes smoked per day in the marijuana and nicotine using group appears to be related to the severity of hippocampal shrinkage. The greater the number of cigarettes smoked per day, the smaller the hippocampal volume and the greater the memory performance. There were no significant associations between hippocampal size and memory performance in individuals who only use tobacco or only use marijuana.

“Approximately 70% of individuals who use marijuana also use tobacco,” explained Francesca Filbey, Ph.D., the study’s principal investigator and Director of Cognitive Neuroscience of Addictive Behaviors at the Center for BrainHealth. “Our findings exemplify why the effects of marijuana on the brain may not generalize to the vast majority of the marijuana using population, because most studies do not account for tobacco use. This study is one of the first to tease apart the unique effects of each substance on the brain as well as their combined effects.”

Dr. Filbey’s research team used magnetic resonance imaging (MRI) to examine the hippocampus; an area of the brain that is know to have altered size and shape in association with chronic marijuana use. Participants completed a substance use history assessment and neuropsychological tests three days prior to an MRI head scan. The team compared four groups: nonusers (individuals who have not had any marijuana or tobacco in the past three months), chronic marijuana users (individuals who use marijuana at least four times per week), frequent nicotine users (10 or more times daily) and chronic marijuana plus frequent nicotine users (at least four marijuana uses per week and 10 or more nicotine uses per day).

“We have always known that each substance is associated with effects on the brain and hypothesized that their interaction may not simply be a linear relationship. Our findings confirm that the interaction between marijuana and nicotine is indeed much more complicated due to the different mechanisms at play,” said Filbey. “Future studies need to address these compounding effects of substances.”

She continued, “The combined use of marijuana and tobacco is highly prevalent. For instance, a ‘blunt’ is wrapped in tobacco leaf. A ‘spliff’ is a joint rolled with tobacco. We really need to understand how the combined use changes the brain to really understand its effects on memory function and behavior.”

How scientists study the effects of marijuana on the brain is changing. Until recently marijuana research largely excluded tobacco users from its participant pool, but scientists have found reason to abandon this practice, uncovering significant differences in the brains of individuals who use both tobacco and marijuana and the brains of those who only use marijuana.