by Seshata on 23/07/2014 | Medicinal

Does Cannabis Use Lead to Poor Memory?

The association between cannabis use and poor memory is age-old, and is so prevalent that it has been adopted as part of the standard stereotyping of cannabis users. Various studies have also indicated a connection—but could cannabis also help to improve memory in certain circumstances, such as in cases of brain injury.


How cannabis affects memory

A graphic depicting the human brain. The hemispheres are separated by colours. The prefrontal cortex is indicated, by a red line, as the large left most hemisphere.

There have been dozens of studies into the relationship between cannabis use and memory impairment. It is generally accepted that acute cannabis intoxication causes impairment of short-term episodic and working memory, which is thought to persist for several weeks subsequent to consumption. However, a handful of studies have found little to no significant effect; as impairments are thought to be dependent on various factors including the ratio of cannabinoids, duration and frequency of use, it may be that differences in methodology account for these inconsistent results.

There are indications that cannabis-induced impairment to working memory disproportionately affects women, with heavier users experiencing greater impairment than light users. This fact should be taken into consideration in future studies, and men and women should be investigated separately to establish the most accurate results. The fact that several studies have found no statistical significance in the relationship between memory and cannabis use may be due to the fact that women were underrepresented in these studies—a problem that plagues many investigations into use of psychoactive substances, which on the whole are more widely used by men.

With chronic, heavy cannabis use, it appears that short-term episodic and working memory is more deeply affected than in those that infrequently consume cannabis. The effects on long-term memory are less well established; some studies indicate little long-term impairment, while others indicate the reverse. Age may play a part in determining the extent of long-term impairment—some studies have indicated that adolescents are more likely to suffer long-term effects due to functional changes in the developing brain that may be caused by early cannabis use.

Brain activation on cannabis

Magnetic resonance imaging and similar techniques have revealed that when intoxicated by cannabis, humans utilise different areas of the brain to complete tasks associated with learning, retention of information, and memory.

An anatomical illustration of the human brain as seen from below with the Parahippocampal gyrus highlighted in blue.

A study published in 2006 concluded that cannabis users display lower brain activity than non-users in certain regions involved in associative learning, particularly the parahippocampal regions and prefrontal cortex, despite performing normally in learning tasks. Analysis of the parahippocampal regions revealed no structural differences between cannabis users and non-users. Thus, lower brain activity and resultant memory impairment may not signify damage to neural tissues, but may be the result of a separate variable associated with cannabis use, such as changes in cerebral blood flow.

A separate study also indicated significant impairment in learning and memory performance on a task which is known to activate the hippocampal region, while also demonstrating non-significant differences on a task designed to activate both the hippocampal region and the temporal and prefrontal cortices. The study also indicated that cannabis users had significantly lower activity in the cortices, but significantly higher activity in the right parahippocampal gyrus. It is thought that hyperactivity in the parahippocampal regions is a compensatory process mediating hypoactivity caused by cannabis use in the prefrontal and temporal cortices. Thus, memory tasks primarily involving the parahippocampal region are likely to be more affected in cannabis users than those that utilise the cortices too.

It is well-known that learning and memory acquisition are largely controlled by complex interactions between the prefrontal and temporal cortices and the parahippocampal and hippocampal regions; although their respective roles are not fully understood, it is though that the cortices are primarily involved in declarative memory (consciously recalled facts, knowledge and events), while the hippocampal regions are associated with procedural memory (subconscious, automatically-retrieved memories such as riding a bicycle).

CB1-receptor antagonists and memory

Cannabidiol is thought to mitigate the memory-impairing effects of THC by binding to the CB1-receptor and rendering it inactive. Ligands which bind to but do not activate receptors are known as antagonists; beyond THC, various other cannabinoids have been identified as CB1-receptor antagonists.

The synthetic CB1-receptor antagonist SR141716, also known as rimonabant, has been found on more than one occasion to counteract memory impairment caused by THC. As well as THC, it has also been shown to counteract the inhibition of long-term potentiation (a process that strengthens the connections between neurons established during learning and contributes greatly to the overall process of memory formation) in the hippocampal region induced by the presence of the endogenous CB1-receptor agonist anandamide and the synthetic agonist WIN 55,212-2. Separate research has confirmed that anandamide itself has a similar memory-impairing effect to that of THC.

Cannabidiol and memory

Several studies have indicated that THC adversely affects memory, while cannabidiol actually mediates this effect, by binding to the CB1 receptors and causing them to be unaffected by the presence of THC molecules. A study from 2010 investigated the cannabinoid content of samples collected from study participants, all frequent users, and compared the results of memory and learning tests of individuals using high-CBD varieties against those using low-CBD varieties. THC content of all samples was found to be consistent.

A schematic representation of the two state-model of CB1 receptor activation, in which receptors are in equilibrium between two states, active and inactive (R* and R).

Users consuming low-CBD varieties (containing less than 0.14% CBD) showed significant impairment in memory tasks at the time of intoxication, while those consuming high-CBD varieties (containing more than 0.75% CBD) showed no impairment, indicating that CBD’s antagonistic effect on the CB1 receptor mitigates the memory-impairing effect of THC.

A separate study into rats showed that high-CBD extracts had no effect on working and short-term memory, even in the presence of high concentrations of THC. However, when additional THC was administered, high-CBD-rich extracts did not reverse subsequent memory impairment. Thus, it appears that impairment of working and short-term memory is dependent on the ratio between CBD and THC.

CBD and perinatal brain injury

CBD has been shown to provide a neuroprotective influence on newborn rats subject to hypoxia-ischemia, a common cause of perinatal brain injury that can severely affect learning and memory consolidation. CBD mitigates inflammation levels and reduces oxidative stress subsequent to brain injury, preventing cell death and reducing the extent of tissue damage compared to controls, thereby enabling developmental processes and allowing the individual to achieve greater overall cognitive ability in adulthood.

A separate study demonstrated that young rats subject to memory impairment induced by iron toxicity experienced improvements in memory when treated with CBD upon reaching adulthood, demonstrating that CBD can reverse memory impairment as well as prevent it. If these results can be replicated in humans, it could lead to the development of much-needed additions to the limited range of treatment options currently available for recovery of memory.

Memory improvement in degenerative brain disease

A digital rendering of the hippocampal-neuron, brightly coloured, with multiple branches and globules

In healthy individuals, it appears that THC has significant effects on memory but that CBD helps to mediate this impairment. However, in individuals suffering from certain degenerative diseases, it appears that both THC and CBD can exert a neuroprotective effect, inhibit ongoing impairment of memory, and potentially even assist in improving it.

The potential for cannabinoid therapies to slow the progression of Alzheimer’s and potentially even assist in repairing damaged brain tissue is well-known. Cannabinoid therapies can reduce the persistent inflammation of brain tissues that ultimately leads to neuronal death in Alzheimer’s, as well as assisting in the regulation of glutamatergic transmission, which is crucial to the process of long-term potentiation of memories. Cannabinoids are also known to reduce the characteristic plaques that form in neural tissue as a result of Alzheimer’s.

It appears that THC and other CB1-receptor agonists are the key to this process, as the synthetic cannabinoid WIN 55,212-2 has also been shown to reduce brain tissue inflammation and improve working memory in older rats. Another similar study indicated that older rats also underwent neurogenesis (growth of new neural cells) in the hippocampus when treated with WIN 55,212-2, as well as showing marked improvements in cognitive abilities.

As well as THC and CBD, there may be other compounds contained within cannabis that can assist in memory improvement in degenerative brain disease. Terpenoids and flavonoids found in various plant species have been shown to improve memory in Alzheimer’s patients; while no specific research into cannabis terpenoids and Alzheimer’s exists, it is likely that some exert a specific effect of their own.

Importance of THC in forgetting

While much is made of cannabis’ ability to impair memory, this property could also be useful in medicine. A little-considered potential application for THC in medicine is in the suppression or erasure of negative or traumatic memories, such as in those affected by post-traumatic stress disorder (PTSD).

Acquisition and retention of negative memories is a crucial part of learning to avoid danger by developing behavioural responses. If a negative experience occurs repeatedly, the response is consolidated and becomes instinctive. Without such reinforcement, the response diminished over time until it is non-existent—but in individuals subject to severe, repeated trauma, the response does not diminish even when the original stimulus is no longer present.

A digital illustration showing a translucent blue figure from the front and their brain inside their head. The Hippocampus is brightly illuminated.

As our understanding of the role of the endocannabinoid system (particularly the CB1-receptor) in memory and learning grows, it is becoming clear that it is crucial to the extinction of aversive memories. A study published in 2002 demonstrated that mice deficient in CB1-receptors exhibited reduced ability to extinguish aversive memories when subjected to fear-conditioning tests, while showing no impairment in learning or memory acquisition. Activation of the CB1-receptorby an agonist such as anandamide is crucial to the extinction of memories; thus, THC is likely to be useful in the long-term management of PTSD and related disorders.

While the old stereotype that cannabis use leads to impaired memory generally appears to hold true, it is clear that the relationship between the endocannabinoid system, learning and memory is highly complex and cannot be broken down so simplistically. In normal conditions, the actions of THC do impair memory, but these effects are mitigated and potentially cancelled out entirely by the presence of CBD in certain ratios. Furthermore, THC and CBD, and other cannabis compounds may exert neuroprotective effects in degenerative brain disease and injury, and may assist in memory recovery. CBD may reverse memory loss caused by brain injury even when administered months after the initial trauma. Clearly, more research is needed to establish the precise interactions between the various cannabinoids, so that much-needed new therapies can be developed.

Comment Section

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Dan

THC only makes you forget things which don't matter anyway.

24/07/2014

maxwood

"Heavy use" may be code language for exposure to carbon monoxide and other combustion toxins which could be expected to affect memory, but which can be avoided by vaporizing instead of "smoking" the herb. More research needed on alternative delivery systems when used instead of H-ot B-urning O-verdose M-onoxide rolling papers.

25/07/2014

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