Taxing Cannabis

Taxing Cannabis = £6.5 b

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Monday, 24th July 2017

Cannabis

Cannabis & Memory Function


The effects of cannabis on short-term memory are long-established, users consistently perform worse than matched controls on laboratory tests of memory.  Scientific research has focussed on the role of endocannabinoids in regulating memory processes.

 

For this report a Medline search using keywords cannabi* and memory identified a total of 725 scientific papers, this review concentrates on human studies.

 

 

Anecdotal studies and case reports

Shukla & Moore[i] describe the case of a 6 year old boy who developed transient global amnesia after accidentally eating a cannabis-laced cookie, noting “Transient global amnesia as a result of marijuana intoxication is an extremely rare event.”

 

In a forensic case study, Niveau[ii] reported an offence committed during a cannabis flashback, cautioning “the possible participation of flashback phenomena must not be neglected when grounds of unexplained accidents or crimes are searched”, however Fischer & Täschner[iii] reported “A definite correlation between the amount of hashish consumed and the occurrence of flashback does not exist. Flashbacks have also been reported after consuming cannabis alone. However, data vary regarding the frequency of such flashbacks. According to the available data they occur rarely and require a thorough differential diagnostic evaluation in each individual case. As a rule, the occurrence of a flashback may take place in cases where there is an intake of hallucinogenic drugs in the recent case history

 

Population studies

Schweinsburg et al[iv] reported “(Marijuana-using) teens showed abnormalities in brain response during a (spatial working memory) task compared with controls, even after 1 month of abstinence.” and further noted[v]Adolescents demonstrate persisting deficits related to heavy marijuana use for at least six weeks following discontinuation, particularly in the domains of learning, memory, and working memory.”

 

From a population-based study of 284 young adults with moderate lifetime cannabis use, Indlekofer et al[vi] reported “Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner.” In a survey of cannabis use by Spanish secondary school pupils, Morales et al[vii] found “The most frequently reported effects were memory loss, sadness and difficulties in studying or working.”

 

Heavy/long term/dependent users

Studying abstinent but frequent cannabis-using adolescent boys in the Netherlands and USA, Jager et al[viii] found “Cannabis users performed normally on both memory tasks. During (working memory) assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on (associative memory)-related brain function was found.”  Investigating long-term heavy users seeking treatment, Solowij et al[ix] reported “Long-term cannabis users performed significantly less well than shorter-term users and controls on tests of memory and attention.”

 

Fernandez-Serrano et al[x] reviewing human studies of chronic users, noted that cannabis (and other drugs) were “commonly associated with significant alterations in the neuropsychological domains of episodic memory, emotional processing, and the executive components of updating and decision-making. …cannabis (use affected) processing speed and complex planning. The magnitude of both generalized and specific neuropsychological effects is overall attenuated in samples achieving long-term abstinence,”  Studying long-term cannabis users, Battisti et al[xi] noted “relative to non-using controls, chronic users of cannabis have altered memory-related brain activation in the form of dysfunctional SME production and/or poorer neural efficiency, which is associated with deficits in memory recall. Greater alteration was associated with a longer history of cannabis use and an earlier onset of use. Neuroadaptation to the effects of chronic exposure may additionally play a role.”

 

Roser et al[xii] compared light and ‘heavy’ (15+ joints per week) cannabis users with controls on tests of auditory memory and processing, concluding “chronic cannabis use may cause a specific impairment of auditory information processing”  Morgan et al[xiii] found cannabis users under the influence to have semantic memory impairments compared to control subjects  Messinis et al[xiv] examined neuropsychological functioning in 20 long-term (LT), 20 shorter term (ST) heavy frequent cannabis users, and 24 controls after 24 hrs abstinence, finding “LT users performed significantly worse on verbal memory and psychomotor speed. LT and ST users had a higher proportion of deficits on verbal fluency, verbal memory, attention, and psychomotor speed.”

 

Pope et al[xv] looked at light and heavy cannabis users of both sexes and noted “marked and significant differences were found between heavy- and light-smoking women on the subtest examining visuospatial memory... The heavy-smoking women remembered significantly fewer squares on this test, and they made significantly more errors than the light-smoking women” Pope et al[xvi] found “Heavy users displayed significantly greater impairment than light users on attention/executive functions, as evidenced particularly by greater perseverations on card sorting and reduced learning of word lists” noting[xvii]The data support a 'drug residue' effect on attention, psychomotor tasks, and short-term memory during the 12-24 h period immediately after cannabis use, but evidence is as yet insufficient to support or refute either a more prolonged 'drug residue' effect, or a toxic effect on the central nervous system that persists even after drug residues have left the body.”

 

Studying long-term users in Costa Rica, Fletcher et al[xviii] found “Older long-term users performed worse than older nonusers on 2 short-term memory tests involving learning lists of words. In addition, older long-term users performed worse than older nonusers on selective and divided attention tasks associated with working memory. No notable differences were apparent between younger users and nonusers… Long-term cannabis use was associated with disruption of short-term memory, working memory, and attentional skills in older long-term cannabis users.” Soueif[xix], studying performance on neurological tests of long term heavy users in Egypt, found “The older the subject the smaller the amount of function deficit associated with cannabis consumption

 

In a study of attitudes among long-term users, Gruber et al[xx] reported “When asked to rate the subjective effects of cannabis on their cognition, memory, career, social life, physical health and mental health, large majorities of heavy users (66-90%) reported a 'negative effect'.”  In a web-based survey of self-reported memory problems among users of cannabis and/or ecstasy, Rodgers et al[xxi] reported “We found that cannabis was associated with reports of 'here-and-now' cognitive problems in short-term and internally cued prospective memory. In contrast, Ecstasy was associated with reports of long-term memory problems, which were more related to storage and retrieval difficulties.”

 

IDMU Survey data:

In our 1994-1998 surveys with results analysed for the House of Lords cannabis enquiry[xxii], ‘memory problems’ (170x reports, 6.1%) was the most common symptom reported in open-response reports to “have you suffered physical or mental health problems from cannabis use – if Yes what problems?”  There was no relationship between incidence of memory problems and age of initiation to cannabis use, but there were highly significant associations with frequency of cannabis use, and with frequency of using other drugs including stimulants, hallucinogens, tobacco, alcohol, ecstasy and tranquillisers.

 

In our 1999 survey, respondents were asked to rate the severity and frequency of named problems, for memory problems although 43% of respondents reported experiencing these to some degree, only 3% reported severe problems, 20% reporting regular problems and 4% reporting continual/ongoing problems (Table 9)

 

Frequency & Severity of Memory Problems among Regular Cannabis Users (1999)

Frequency

n

%

Severity

n

%

Once or twice

232

10.7%

Mild

464

21.4%

Occasionally

392

18.0%

Moderate

313

14.4%

Regularly

223

10.3%

Severe

68

3.1%

All the time

84

3.9%

Total

845

38.9%

Total ever

931

42.8%

Base

2173

100.0%

Users of alcohol and other drugs

Studying users of ecstasy and/or cannabis, Dafters et al[xxiii] reported “cannabis users, whether or not they also used MDMA, showed significantly impaired memory function on word free-recall and on immediate and delayed story recall compared to non-users”  Croft et al[xxiv] noted “The cannabis and MDMA/cannabis groups did not differ on any of the tests, whereas the combined cannabis and MDMA/cannabis groups performed more poorly than controls on tests of memory, learning, word fluency, speed of processing and manual dexterity”

 

Comparing users of ecstasy only, cannabis only and controls Rodgers[xxv] reported “Performance was similar across all three groups for measures of visual reaction time, auditory reaction time, complex reaction time, visual memory and attention and concentration. Significant impairment was found on measures of verbal memory in both cannabis users and ecstasy users.”  Gouzoulis-Mayfrank et al[xxvi] reported “Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users.”

 

Fisk & Montgomery[xxvii] found “Relative to nonusers, cannabis users were found to be impaired in several aspects of real world memory functioning.”  They earlier reported from a study of ecstasy users and everyday memory[xxviii] (e.g. remembering to do something in the future): “cannabis emerged as the only significant predictor of everyday and prospective memory deficits. Significant correlations were found between the different indicators of everyday memory and various measures of illicit drug use. Cannabis featured prominently in this respect. The present study provides further support for cannabis related deficits in aspects of everyday memory functioning.”

 

Psychiatric patients

DeRosse et al[xxix] found schizophrenia patients who used cannabis showed better performance in memory and cognitive functions than those who did not.  Yucel et al[xxx] also found first-episode psychosis patients with a history of cannabis use “performed better on tests of visual memory, working memory, and executive functioning (than nonusing patients). Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients.”  De la Serna et al[xxxi] found similar results with cannabis-related psychotic patients (CU) performed better on tests of cognition, attention and memory than non-using psychotic patients.

 

Studying schizophrenia patients, Scholes & Martin-Iverson[xxxii] found “little difference in cognitive performance between cannabis users and non-users, suggesting that cannabis use has only subtle effects on the neurocognitive performance indices assessed”  Ringen et al[xxxiii] found “In bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p=0.019), executive functioning (verbal fluency--set shifting) (p=0.009), logical memory-learning (p=0.007) and on logical memory-recall (p=0.004).”  Mata et al[xxxiv] concluded “Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis” Similar results showing improved performance have been reported by Schnell et al[xxxv], Coulston et al[xxxvi], Potvin et al[xxxvii], D’Souza et al[xxxviii], Liraud & Verdoux[xxxix]

 

In subjects with Tourettes syndrome, Müller-Vahl et al[xl] noted “During medication and immediately as well as 5-6 weeks after withdrawal of Delta(9)-THC treatment, no detrimental effect was seen on learning curve, interference, recall and recognition of word lists, immediate visual memory span, and divided attention. Measuring immediate verbal memory span, we even found a trend towards a significant improvement during and after treatment.” Müller-Vahl et al [xli] also reported “we found no significant differences after treatment with delta9-THC compared to placebo treatment in verbal and visual memory, reaction time, intelligence, sustained attention, divided attention, vigilance, or mood. Only when using the Symptom Checklist 90-R (SCL-90-R) did our data provide evidence for a deterioration of obsessive-compulsive behavior (OCB) and a trend towards an increase in phobic anxiety.”

 

In a genetic study of patients with psychosis, their family members and healthy controls, Henquet et al[xlii] found that carriers of the gene predicting psychotic reactions to cannabis “were also more sensitive to Delta-9-THC-induced memory and attention impairments”  Di Forti et al[xliii] observed “Heavy cannabis use has… been shown to affect memory and learning performance, both in healthy individuals and in patients suffering from psychosis

 

Controlled studies

Comparative studies:

Comparing verbal memory test results from adolescent cannabis users to matched alcohol users and non-using controls Solowij et al[xliv] noted “Cannabis users performed significantly worse than alcohol users and non-users on all performance indices. They recalled significantly fewer words overall (p < 0.001), demonstrating impaired learning (p < 0.001), retention (p < 0.001) and retrieval (p < 0.05) (Cohen's d 0.43-0.84). The degree of impairment was associated with the duration, quantity, frequency and age of onset of cannabis use, but was unrelated to alcohol exposure or other drug use.”

 

Investigating the effects of antipsychotic drugs combined with cannabis on healthy controls and frequent cannabis users, D’Souza et al[xlv] reported “Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Delta-9-THC. Haloperidol and Delta-9-THC worsened distractibility and vigilance.”  Their earlier study[xlvi] found frequent cannabis use to be associated with “impaired memory and attention” but noted “frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.”

 

Prospective Memory:

Studying prospective memory performance in cannabis using and non-using students, Bartholomew et al[xlvii] found “no significant differences in the number of self-reported prospective memory failures; however, cannabis users recalled significantly fewer location-action combinations than non-users in the video-based prospective memory task (suggesting) that cannabis use has a detrimental effect on prospective memory ability in young adults but users may not be aware of these deficits.”  McHale & Hunt[xlviii] compared performances of short-term abstinent cannabis users with tobacco-using and standard controls, finding “The cannabis users, compared to both control groups, had deficits on verbal fluency, visual recognition, delayed visual recall, and short- and long-interval prospective memory. There were no differences for immediate visual recall.” Comparing current cannabis users to controls, Nestor et al[xlix] reported “cannabis users were significantly worse with respect to learning, short and long-term memory performance

 

Short-Term memory:

Studying short-term memory in adolescents, Schwarz et al[l] reported “Significant differences between the cannabis-dependent group and the two control groups were obtained initially on the Benton Visual Retention Test (F[2,24] = 6.07) and the Wechsler Memory Scale Prose Passages (F[2,23] = 7.04). After 6 weeks of supervised abstention from intoxicants, subjects in the cannabis-dependent group showed some significant improvement on the Wechsler Memory Prose Passages score and on the Benton Visual Retention Test; however, the improvement failed to achieve statistical significance. We concluded that cannabis-dependent adolescents have selective short-term memory deficits that continue for at least 6 weeks after the last use of marijuana.”

 

Melges et al[li] reported “High oral doses of marihuana extract, calibrated for content of 1 (-)-Delta(1)-tetrahydrocannabinol, significantly impaired the serial coordination of cognitive operations during a task that required sequential adjustments in reaching a goal. This disintegration of sequential thought is related to impaired immediate memory.”  In tests of reaction times and short-term memory performance Rossi et al[lii] noted “no statistically significant differences between control and marihuana performance

 

Working Memory:

Harvey et al[liii] reported “Adolescents who were regular cannabis users (more than once a week) had a significantly poorer performance on four measures of cognitive function reflecting attention, spatial working memory and learning. Cannabis use remained an independent predictor of performance on the working memory and strategy measures after additional predictor variables were included in a multivariate regression analysis.” Wadsworth et al[liv] studied associations between cannabis use and cognitive performance, mood and human error at work, finding “Cannabis use was associated with impairment in both cognitive function and mood, though cannabis users reported no more workplace errors than controls. Cannabis use was associated with lower alertness and slower response organization. In addition, users experienced working memory problems at the start, and psychomotor slowing and poorer episodic recall at the end of the working week.

 

Ilan et al[lv] compared effects on working and episodic memory of marijuana and placebo, reporting “Responses in the (working memory) task were slower and less accurate after smoking marijuana, accompanied by reduced alpha band EEG reactivity in response to increased task difficulty. In the (episodic memory) task, marijuana was associated with an increased tendency to erroneously identify distracter words as having been previously studied. In both tasks, marijuana attenuated stimulus-locked event-related potentials (ERPs).”

 

Verbal Memory:

Comparing memory performance during nicotine withdrawal among adolescent abstinent-users and nonusers of cannabis, Jacobsen et al[lvi] found “Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects”. Belmore & Miller[lvii] reported “subjects recalled fewer words while intoxicated with marijuana… Drug subjects were more likely to forget meaningfully processed words on recently presented lists.”  Miller et al[lviii] reported “marijuana significantly decreased immediate and final free recall but only slightly influenced recognition memory. Rate of acquisition on the repeated lists was the same for both groups. Long term retention of encoded information was not influenced by marijuana

 

In a prose-retrieval task using a randomized crossover design, Miller et al[lix] noted “Results indicated that marijuana reduced immediate recall under both cued and uncued conditions incomparison to placebo. No relative cued recall advantage was found in the marijuana groups for the old or new story and marijuana produced only a moderate decrement in recall of the old story on day two. However, marijuana given in the second phase significantly reduced memory for items recalled in the initial phase irrespective of drug or cueing condition in phase one, suggesting that retrieval was also affected.” They also reported[lx]Results indicated that recall was depressed following marijuana administration under both cued and uncued conditions with cues being only mildly effective in reversing the recall deficit. There was no increase in the number of internal intrusions under marijuana, but the number of external intrusions was significantly elevated under the cued conditions.”

 

Digit recall:

Studying residual effects of cannabis, Heishman et al[lxi] reported “Performance was… impaired (decreased accuracy and increased response time) on serial addition/subtraction and digit recall tasks on day 1 in two subjects. On day 2, … subjective effects of marijuana were not observed. Performance remained impaired on the arithmetic and recall tasks on day 2, although the decrements were not as large as those observed on day 1.” Varma et al[lxii] reported “Compared with a control group, the cannabis users were found to react slowly in perceptuo-motor tasks, but not to differ in intelligence or memory tests.”

 

Memory Intrusions:

Hooker & Jones[lxiii] found “A significantly greater number of short story omissions and intrusions occurred in delayed free recall after marijuana. Immediate and sustained attention, controlled retrieval from semantic memory, and speed of reading and naming colors were not affected.” In a study of memory intrusions Pfefferbaum et al[lxiv] found “marijuana and the association-rehearsal procedure reduced the number of correct recalls and increased the number of intrusions (nonlist items which were incorrectly recalled as having been on the list to be learned). The intrusions were divided into three categories: a) words found on prior lists; b) associates spoken during the rehearsal; or c) totally new works not previously mentioned. Marijuana significantly increased the number of new intrusions

 

Remote/Long-Term Memory:

Wetzel et al[lxv] studied effects of cannabis on remote (long-term) memory, finding “Marijuana did not affect remote memory in comparison to placebo...  Marijuana significantly impaired new learning at the same time that remote memory was unaffected.”  Darley et al[lxvi] noted “Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication.”  Abel[lxvii] found “marihuana did not affect retrieval of information in memory when the method of free recall was used, but did affect recognition processes such that subjects were less able to discriminate between items that had been presented previously and items that had not appeared a short time before. With respect to initial learning, marihuana was shown to affect acquisition processes involved in the storage of information.”

 

Medicinal Uses & Therapeutic Research

Studying the effect of 1-3mg nabilone in healthy volunteers, Wesnes et al[lxviii] found “Impairments to attention, working and episodic memory and self-ratings of alertness were evident”  Studying nabilone treatment for MS patients, Kurtzhaler et al[lxix] reported “Five neuropsychological functions (reaction time, working memory, divided attention, psychomotor speed and mental flexibility) were assessed. No indication was found of a deterioration of any of the five investigated neuropsychological functions during the 4-week treatment period with nabilone.”

 

Pertwee[lxx] reviewing potential clinical applications of cannabinoids, noted “CB1 receptor antagonists may also have clinical applications, e. g. as appetite suppressants and in the management of schizophrenia or disorders of cognition and memory.”  Grotenhermen[lxxi] concluded “long-term impairment of memory, attention, and complex cognitive processes are low and do not preclude a legitimate therapeutic use”


In a clinical trial of cannabis-based oral-spray medicine in MS patients, Rog et al[lxxii] noted “Cognitive side effects were limited to long-term memory storage” in HIV patients receiving cannabinoid therapy Woolridge et al[lxxiii] found “Many cannabis users (47%) reported associated memory deterioration.”

 

Different types/strength of cannabis

Cannabidiol (CBD):

Morgan et al[lxxiv] tested memory function in users smoking their own cannabis which was tested for THC and CBD content, finding “Groups did not differ in the THC content of the cannabis they smoked. Unlike the marked impairment in prose recall of individuals who smoked cannabis low in cannabidiol, participants smoking cannabis high in cannabidiol showed no memory impairment.”  Comparing effects of THC and CBD, Bhattarchaya et al[lxxv] found “Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task

 

In a study comparing the effects of cannabis with different cannabinoid profiles, Ilan et al[lxxvi] reported “Compared to placebo, active THC cigarettes produced expected effects on mood, behavior and brain activity. A decrease in performance, reduction in EEG power and attenuation of ERP components reflecting attentional processes were observed during tests of working memory and episodic memory. Most of these effects were not dose-dependent. Varying the concentrations of CBC and CBD did not change subjects' responses on any of the outcome measures.”  Nicholson et al[lxxvii] compared effects of different dosages and cannabinoid profiles on sleep in volunteers, finding “The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood… 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.”

 

Menhiratta et al[lxxviii] compared bhang drinkers with charas smokers, exposed to an average 150mg THC per day, and matched controls, noted “Charas smokers were the poorest performers and also showed poor memory

 

THC dosage:

Testing effects of cannabis cigarettes with varying THC contents (up to 69mg) on regular but not daily users, Hunault et al[lxxix] found “The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks.”   Comparing effects of low, high dose THC with placebo in volunteers, D’Souza et al[lxxx] found THC: “disrupted immediate and delayed word recall, sparing recognition recall; impaired performance on tests of distractibility, verbal fluency, and working memory” In a small study of low and high dose THC on working memory, Lane et al[lxxxi] reported “both delta9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination

 

Curran et al[lxxxii] tested different doses of oral THC and placebo on memory, finding “Delta(9)-THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration (2 h post-drug). At the same time point, performance on an implicit memory task was preserved intact. The higher dose of delta(9)-THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by delta(9)-THC… oral delta(9)-THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory” Klonoff et al[lxxxiii] tested low and high dose marijuana on neuropsychological tests, finding “The low dose produced generalized impairment of all mental processes (concept formation, memory, tactile form discrimination and motor function) and the effect was generalized to all modalities. The high dose resulted in more extensive impairment, again generalized… The effects of marijuana on learning as well as memory were explained in terms of impaired output (recall), but the impairment was transient.”

 

Fundamental brain & receptor research

In a brain-imaging study of associative memory in cannabis users and controls, Jager et al[lxxxiv] found “Cannabis users displayed lower activation than non-users in brain regions involved in associative learning, particularly in the (para)hippocampal regions and the right dorsolateral prefrontal cortex, despite normal performance… lower brain activation… could be the expression of a non-cognitive variable related to frequent cannabis use, for example changes in cerebral perfusion or differences in vigilance”.  Chang et al[lxxxv] reported “Despite similar task and cognitive test performance compared with control subjects, active and abstinent marijuana users showed decreased activation in the right prefrontal, medial and dorsal parietal, and medial cerebellar regions, but greater activation in various frontal, parietal and occipital brain regions during the visual-attention tasks (all with P < or = 0.001, corrected, cluster level).”  Jager et al[lxxxvi] noted “Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex.” Kanayama et al[lxxxvii] found “Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate)… Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

 

Ashtari et al[lxxxviii] found lower right hippocampal volumes and impaired memory performance compared to matched controls among adolescents with a prior history of ‘heavy’ (5.8 joints/day) cannabis use who had been abstinent for an average 6.7 months, concluding “These findings… lend support to a theory that cannabis use may impart long-term structural and functional damage.”  Demirakca et al[lxxxix] noted “Lower volume in the right hippocampus in chronic cannabis users was corroborated. Higher THC and lower CBD was associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD.”  Becker et al[xc] found no performance differences between occasional and regular users except that regular use was associated with “increased activity in the left parahippocampal gyrus”  Irving et al[xci] concluded “Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory” Sullivan[xcii] concluded “Cannabinoids reduce glutamate release through a G-protein-mediated inhibition of the calcium channels responsible for neurotransmitter release from hippocampal neurons. These mechanisms likely play a role in the learning and memory impairments produced by cannabinoids and by endogenous cannabinoid receptor ligands.”

 

Varvel et al[xciii], reviewing animal studies of cannabinoid receptor effects on memory, reported “Several groups have reported that CB(1) receptor antagonists enhance memory duration in a variety of spatial and operant paradigms, but not in all paradigms. Conversely, disruption of CB(1) receptor signaling also impairs extinction learning in which the animal actively suppresses a learned response when reinforcement has been withheld”  Laaris et al[xciv] concluded “Marijuana impairs learning and memory through actions of its psychoactive constituent, delta-9-tetrahydrocannabinol (Delta(9)-THC), in the hippocampus, through activation of cannabinoid CB1 receptors (CB1R). CB1Rs are found on glutamate and GABA neuron axon terminals in the hippocampus where they control neurotransmitter release.”  Studying the effect of CB1-receptor antagonist on affective memory in healthy volunteers, Horder et al[xcv] found “rimonabant selectively reduced incidental recall of positive self-relevant adjectives. …a single dose of rimonabant decreases positive emotional memory in the absence of changes in subjective state

 

Hampson & Deadwyler[xcvi] concluded “A possible role for cannabinoid receptors and endogenous cannabinoids may thus be to regulate the storage (i.e., encoding) of information, as well as the means by which that information is retrieved.”

 

Short or long-term effects?

McGuinness[xcvii] stated cannabis use to cause “memory problems that may persist for a month after last use” Nahas & Latour[xcviii] stated “Clinical manifestations of pathophysiology due to marijuana smoking are now being reported. These include: long-term impairment of memory in adolescents

Comparing current and former users, Fried et al[xcix] noted “After accounting for potentially confounding factors and pre-drug performance in the appropriate cognitive domain, current regular heavy users did significantly worse than non-users in overall IQ, processing speed, immediate, and delayed memory. In contrast, the former marihuana smokers did not show any cognitive impairments.”

 

Pope et al[c] investigated whether long-term cognitive deficits are found in abstinent heavy users, reporting “The heavy smokers showed deficits on memory of word lists on Days 0, 1, and 7 of a supervised abstinence period. By Day 28, however, few significant differences were found between users and controls on the test measures, and there were few significant associations between total lifetime cannabis consumption and test performance.”  In older users, Pope et al[ci] also found “At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores.” Pope et al[cii] concluded “deficits in attention and memory persist for at least several days after discontinuing regular heavy cannabis use.”

 

After a longitudinal study of IQ performances in young adults with and without histories of cannabis use, Fried et al[ciii] concluded “marijuana does not have a long-term negative impact on global intelligence.”

 

Reviews

In a 2003 review of animal studies, Castellano et al[civ] noted “It has been shown, for example, that Delta9-THC impairs memory in rats, mice and monkeys tested in a variety of experimental conditions (radial maze, instrumental discrimination tasks, Morris water maze, etc.). In some of these researches the effect of Delta9-THC was antagonized by the CB1 receptor antagonist SR 141716A, showing the involvement of this subtype of cannabinoid receptor in its effect.”

 

2004 reviews:  Kalant[cv] noted “Cognitive impairments of various types are readily demonstrable during acute cannabis intoxication, but there is no suitable evidence yet available to permit a decision as to whether long-lasting or permanent functional losses can result from chronic heavy use in adults. However, a small but growing body of evidence indicates subtle but apparently permanent effects on memory, information processing, and executive functions, in the offspring of women who used cannabis during pregnancy.”  Carlini[cvi] observed “On the cognitive domain it impairs the human capacity to discriminate time intervals and space distances, vigilance, memory and the performance for mental work. On the psychic area Delta(9)-THC may induce unpleasant reactions such as disconnected thoughts, panic reactions, disturbing changes in perception, delusions and hallucinatory experiences.”

 

In 2005 reviews, Riedel & Davies[cvii] observed: “Animal studies, which enable a more controlled drug regime and more constant behavioural testing, have confirmed human results and suggest, with respect to hippocampus, that exogenous cannabinoid treatment selectively affects encoding processes… Administration of exogenous selective CB1 agonists may therefore disrupt hippocampus-dependent learning and memory by 'increasing the noise', rather than 'decreasing the signal' at potentiated inputs.”  Lundqvist[cviii] noted “Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention.”  Karila et al[cix] stated “Amongst the cognitive functions considered, memory-related, attention-related, psychomotor and motivation-related functions were proved deteriorated by acute and chronic cannabis use

 

In 2006 reviews, Ranganathan & D’Souza[cx] noted “Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids.”, Egerton et al[cxi] observed “Effects of cannabinoids on cognition may be mediated via interaction with neurochemical processes in the PFC (pre-frontal cortex) and hippocampus. In the PFC, cannabinoids may alter dopaminergic, cholinergic and serotonergic transmission. These mechanisms may underlie cognitive impairments observed following marijuana intake in humans, and may also be relevant to other disorders of cognition.”

 

In a 2008 review, Solowij & Battisti[cxii] observed “Most recent studies have examined working memory and verbal episodic memory and cumulatively, the evidence suggests impaired encoding, storage, manipulation and retrieval mechanisms in long-term or heavy cannabis users. These impairments are not dissimilar to those associated with acute intoxication and have been related to the duration, frequency, dose and age of onset of cannabis use.”  In 2007 reviews, Grotenhermen[cxiii] concluded “Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users”, Linzen & van Amelsvoort[cxiv] stated “Acute cannabis administration can induce memory impairments, sometimes persisting months following abstinence. There is no evidence that residual effects on cognition remain after years of abstinence… (THC) induces psychotic like states and memory impairments in healthy volunteers.”

 

In a 2010 review, Solowij & Pesa[cxv] observed “Cannabis use impairs memory, attention, inhibitory control, executive functions and decision making, both during the period of acute intoxication and beyond, persisting for hours, days, weeks or more after the last use of cannabis… Long-term or heavy cannabis use appears to result in longer-lasting cognitive abnormalities and possibly structural brain alterations.”

 

Summary – Cannabis & Memory

There is compelling evidence that acute cannabis intoxication causes dose-related deficits in most aspects of memory including encoding, storage and retrieval.  Such deficits may be offset where cannabis contains significant levels of CBD.  This effect is well-established and research into the endocannabinoid system is currently leading recent developments in understanding of memory processes. Such deficits are typically measured by laboratory tests including, for example, verbal recall or symbol matching, where small but consistent deficits can achieve statistical significance.   A small minority of users report severe memory problems.

 

The evidence suggests that in the majority of cases, memory deficits do not persist during long periods of abstinence from the drug. Long-term users can learn mitigate the deficits by novel strategies and by using different brain pathways to encode information.

 

There are few reports of the effects on episodic memory, but errors of omission and even addition have been reported, tending to reflect smaller details rather than major blackouts or inventions.  The few studies of long-term episodic memory find only weak associations between cannabis use and long-term memory deficits, which tend to include forgetting (particularly in cases of post-traumatic stress).

 

Also Read: Effects of Cannabis on Memory & Cognitive Function

 


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