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Adverse Effects of Cannabis - Hall Solowij

Adverse Effects of Cannabis - Hall Solowij

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Published by PRMurphy
"Psychosis: Large doses of THC produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation.44 Such reactions are rare, occurring after unusually heavy cannabis use; in most cases they remit rapidly after abstinence from cannabis.2 There is an association between cannabis use and schizophrenia. A prospective study of 50 000 Swedish conscripts45 found a dose-response relation between the frequency of cannabis use by age 18 and the risk of a diagnosis of schizophrenia over the subsequent 15 years. A
plausible explanation is that cannabis use can exacerbate the symptoms of schizophrenia,2,46 and there is prospective
evidence that continued use predicts more psychotic symptoms in people with schizophrenia.47"
"Psychosis: Large doses of THC produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation.44 Such reactions are rare, occurring after unusually heavy cannabis use; in most cases they remit rapidly after abstinence from cannabis.2 There is an association between cannabis use and schizophrenia. A prospective study of 50 000 Swedish conscripts45 found a dose-response relation between the frequency of cannabis use by age 18 and the risk of a diagnosis of schizophrenia over the subsequent 15 years. A
plausible explanation is that cannabis use can exacerbate the symptoms of schizophrenia,2,46 and there is prospective
evidence that continued use predicts more psychotic symptoms in people with schizophrenia.47"

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Published by: PRMurphy on Jan 15, 2011
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cannabis is mostly smoked because this is the easiest wayto achieve the desired psychoactive effects.
2
A typical joint contains between 0·5 g and 1·0 g of cannabis. The THCdelivered varies between 20% and70%,
2
its bioavailability ranging from 5% to 24%.
3
Aslittle as 2–3 mg of available THC will produce a “high”in occasional users, but regular users may smoke five ormore joints a day.Cannabinoids act on a specific receptor that is widelydistributed in the brain regions involved in cognition,memory reward, pain perception, and motorcoordination.
3
These receptors respond to an endogenousligand, anandamide, which is much less potent and has ashorter duration than THC.
3
The identification of aspecific cannabinoid antagonist promises to improve ourunderstanding of the role of cannabinoids in normalbrain function.
3
Patterns of cannabis use
Cannabis has been tried by many European young adultsand by most young adults in the USA and Australia.
1
Most cannabis use is intermittent and time-limited: mostusers stop in their mid to late 20s, and very few engage indaily cannabis use over a period of years.
4
In the USAand Australia, about 10% of those who ever use cannabisbecome daily users, and another 20–30% use the drugweekly.
1,4
Because of uncertainties about THC content, heavycannabis use is generally defined as daily or near dailyuse.
2
This pattern of use over years places users atgreatest risk of adverse health and psychologicalconsequences.
2
Daily cannabis users are more likely to bemale, to be less well educated, to use alcohol and tobaccoregularly, and to use amphetamines, hallucinogens,psychostimulants, sedatives, and opioids.
5
Acute effects of cannabis
Cannabis produces euphoria and relaxation, perceptualalterations, time distortion, and the intensification of ordinary sensory experiences, such as eating, watchingfilms, and listening to music.
2
When used in a socialIn many western societies, cannabis has been used by asubstantial minority, and in some a majority, of youngadults, even though its use is prohibited by law.
1
Debateabout the justification for continuing to prohibit cannabisuse has polarised opinion about the seriousness of itsadverse health effects.
2
In addition, the possibletherapeutic effects of cannabinoids have becomeentangled in the debate about prohibition of recreationalcannabis use (see Further reading). The health effects of cannabis use, especially of long-term use, remainuncertain because there is very little epidemiologicalresearch and because of disagreements about theinterpretation of the limited epidemiological andlaboratory evidence.
2
Here we summarise the evidence onthe most probable adverse health effects of cannabis useacknowledging where appropriate the uncertainty thatremains.
Cannabis the drug
Cannabis preparations are largely derived from thefemale plant of 
Cannabis sativa
. The primarypsychoactive constituent is
-9-tetrahydrocannabinol(THC).
3
The THC content is highest in the floweringtops, declining in the leaves, lower leaves, stems, andseeds of the plant. Marijuana (THC content 0·5–5·0%)is prepared from the dried flowering tops and leaves;hashish (THC content 2–20%) consists of dried cannabisresin and compressed flowers; and hashish oil maycontain between 15% and 50% THC.
3
Sinsemilla andNetherwood varieties of cannabis may have a THCcontent of up to 20%.
3
Cannabis may be smoked in a “joint”, which is the sizeof a cigarette, or in a water pipe. Tobacco may be addedto assist burning. Smokers typically inhale deeply andhold their breath to maximise absorption of THC by thelungs. Marijuana and hashish may also be eaten, but
Adverse effects of cannabis
Wayne Hall, Nadia Solowij 
SEMINAR THELANCET • Vol 352 • November 14, 1998
1611
Lancet 
1998;
352:
1611–16
National Drug and Alcohol Research Centre, University of NewSouth Wales, Sydney 2052, Australia
(W Hall
PhD
, N Solowij (
PhD
)
Correspondence to:
Prof Wayne Hall
Seminar
Cannabis is the most widely used illicit drug in many developed societies. Its health and psychological effects arenot well understood and remain the subject of much debate, with opinions on its risks polarised along the lines of proponents’ views on what its legal status should be. An unfortunate consequence of this polarisation of opinion hasbeen the absence of any consensus on what health information the medical profession should give to patients whoare users or potential users of cannabis. There is conflicting evidence about many of the effects of cannabis use, sowe summarise the evidence on the most probable adverse health and psychological consequences of acute andchronic use. This uncertainty, however, should not prevent medical practitioners from advising patients about themost likely ill-effects of their cannabis use. Here we make some suggestions about the advice doctors can give topatients who use, or are contemplating the use, of this drug.
 
SEMINAR 
setting it may produce infectious laughter andtalkativeness. Short-term memory and attention, motorskills, reaction time, and skilled activities are impairedwhile a person is intoxicated.
2
The most common unpleasant side-effects of occasional cannabis use are anxiety and panic reactions.
2
These effects may be reported by naïve users, and theyare a common reason for discontinuation of use; moreexperienced users may occasionally report these effectsafter receiving a much larger than usual dose of THC.
2
Cannabis smoking or ingestion of THCincreases heartrate by 20–50% within a few minutes to a quarter of anhour; this effect lasts for up to 3 h.
2
Blood pressure isincreased while the person is sitting, and decreased whilestanding.
2
These effects are of negligible clinicalsignificance in healthy young users because tolerancedevelops to them.
2
The acute toxicity of cannabinoids is very low.
2
Thereare no confirmed published cases worldwide of humandeaths from cannabis poisoning, and the dose of THCrequired to produce 50% mortality in rodents is ext-remely high compared with other commonly used drugs.
2
Psychomotor effects and driving 
Cannabis produces dose-related impairments in cognitiveand behavioural functions that may potentially impairdriving a motor vehicle or operating machinery.
6
Theseimpairments are larger and more persistent for difficulttasks that depend on sustained attention.
6
The mostserious possible consequence of acute cannabis use is aroad-traffic accident if a user drives while intoxicated.
2
The effects of recreational doses of cannabis on drivingperformance in laboratory simulators and standardiseddriving courses have been reported by some researchersas being similar to the effects when blood alcoholconcentrations are between 0·07% and 0·10%.
2
However, studies of the effects of cannabis on drivingunder more realistic conditions on roads have shownmuch more modest impairments,
7,8
probably becausecannabis users are more aware of their impairment andless inclined to take risks than alcohol users.
7,8
Results of epidemiological studies of road-trafficaccidents are equivocal because most drivers who havecannabinoids in their blood also have high blood alcoholconcentrations.
2
In two studies with reasonable numbersof individuals who had only used cannabis, there was noclear evidence of increased culpability in these drivers.
9
The separate effects of alcohol and cannabis onpsychomotor impairment and driving performance inlaboratory tasks are roughly additive,
9
so the main effectof cannabis use on driving may be in amplifying theimpairments caused by alcohol, which is often used withthe drug.
2
Effects of chronic cannabis use
Cellular effects and the immune system
Cannabis smoke may be carcinogenic; it is mutagenic invitro and in vivo.
10
Cannabinoids impair cell-mediatedand humoral immunity in rodents, decreasing resistanceto infection, and non-cannabinoids in cannabis smokeimpair alveolar macrophages.
11
The relevance of thesefindings to human health is uncertain because the dosesof THCused in animal studies have been very high, andtolerance may develop to the effects on immunity inhuman beings.
12
A few studies that have pointed to the adverse effects of cannabis on human immunity have not beenreplicated.12 There is no conclusive evidence thatconsumption of cannabinoids impairs human immunefunction, as measured by numbers of T lymphocytes, Blymphocytes, or macrophages, or immunoglobulinconcentrations.12 Two prospective studies of HIV-positive homosexual men have shown that cannabis use isnot associated with an increased risk of progression toAIDS concentrations.13,14David
Respiratory system
Chronic heavy cannabis smoking is associated withincreased symptoms of chronic bronchitis, such ascoughing, production of sputum, and wheezing.
15,16
Lungfunction is significantly poorer and there are significantlygreater abnormalities in the large airways of marijuanasmokers than in non-smokers. Tashkin and colleagues
16,17
have reported evidence of an additive effect of marijuanaand tobacco smoking on histopathological abnormalitiesin lung tissue.Bloom and colleagues
15
reported similar additive effectson bronchitic symptoms in an epidemiological study of the respiratory effects of smoking “non-tobacco”cigarettes in 990 individuals aged under 40 years inTucson, Arizona, USA. Non-tobacco smokers reportedmore coughing, phlegm production, and wheeze thannon-smokers, irrespective of whether they also smokedtobacco. Those who had never smoked any substancehad the best respiratory functioning, followed in order of decreasing function by current tobacco smokers, currentnon-tobacco smokers, and current smokers of bothtobacco and non-tobacco cigarettes. Non-tobaccosmoking alone had a larger effect on respiratory function1612
THELANCET • Vol 352 • November 14, 1998
Figure 1:
Cannabis sativa 
Figure 2:
Resin and dried leaves
   D  a  v   i   d   H  o   f   f  m  a  n   D  a  v   i   d   H  o   f   f  m  a  n
 
than tobacco smoking alone, and the effect of both typesof smoking was additive.
15
In 1997, Tashkin and colleagues
18
reported that therate of decline in respiratory function over 8 years amongmarijuana smokers did not differ from that in non-smokers. This finding contrasted with that of a follow-upof the Tucson cohort,
19
in which there was a greater rateof decline in respiratory function among marijuana-onlysmokers than in tobacco-only smokers and additiveeffects of tobacco and marijuana smoking. Both studiesshowed that long-term cannabis smoking increasedbronchitic symptoms.In view of the adverse effects of tobacco smoking, thesimilarity between tobacco and cannabis smoke, and theevidence that cannabis smoking produceshistopathological changes that precede lung cancer,
17
long-term cannabis smoking may also increase the risksof respiratory cancer.
20
There have been reports of cancers in the aerodigestive tract in young adults with ahistory of heavy cannabis use.
21,22
These reportsareworrying since such cancers are rare amongadultsunder the age of 60, even those who smoketobacco and drink alcohol.
20
Case-control studies of therole of cannabis smoking in these cancers are urgentlyneeded.
Reproductive effects
Chronic administration of high doses of THC to animalslowers testosterone secretion, impairs sperm production,motility, and viability, and disrupts the ovulatory cycle.
23
Whether cannabis smoking has these effects in humanbeings is uncertain because the published evidence issmall and inconsistent.
2
Cannabis administration during pregnancy reducesbirthweight in animals.
24
The results of humanepidemiological studies have been more equivocal.
2
Thestigma of using illicit drugs during pregnancy discourageshonest reporting,
25
and when associations are found, theyare difficult to interpret because cannabis users are morelikely than non-users to smoke tobacco, drink alcohol,and use other illicit drugs during pregnancy, and theydiffer in social class, education, and nutrition.
26
Severalstudies have suggested that cannabis smoking inpregnancy may reduce birthweight.
2
In the bestcontrolled of these studies, this relation has persistedafter statistical control for potential confoundingvariables,
27
but other studies
28
have not shown any suchassociation. The effect of cannabis on birthweight in thestudies that have found an association has been smallcompared with that of tobacco smoking.
26
That cannabis use during pregnancy increases the riskof birth defects is unlikely. Early case reports have notbeen supported by large well-controlled epidemiologicalstudies. For example, the study by Zuckerman et al
27
included a large sample of women with a substantialprevalence of cannabis use that was verified by urineanalysis, and there was no increase in birth defects.There is suggestive evidence that infants exposed inutero to cannabis have behavioural and developmentaleffects during the first few months after birth.
26
Betweenthe ages of 4 and 9 years, children who were exposed inutero have shown deficits in sustained attention,memory, and higher cognitive functioning.
29
The clinicalsignificance of these effects remains unclear since theyare small compared with the effects of maternal tobaccouse.
29
Three studies have shown an increased risk of non-lymphoblastic leukaemia,
30
rhabdomyosarcoma,
31
andastrocytoma
32
in children whose mothers reported usingcannabis during their pregnancies. None of these was aplanned study of the association; cannabis use was one of many potential confounders included in statisticalanalyses of the relation between the exposure of interestand childhood cancer. Their replication is a priority.
Behavioural effects in adolescence 
There is a cross-sectional association between heavycannabis use in adolescence and the risk of leaving high-school education and of experiencing job instability inyoung adulthood.
33
However, the strength of thisassociation is reduced in longitudinal studies whenstatistical adjustments are made for the fact that,compared with their peers, heavy cannabis users havepoor high-school performance before using cannabis.
33,34
There is some evidence that heavy use has adverseeffects on family formation, mental health, andinvolvement in drug-related crime.
33
In each case, thestrong associations in cross-sectional studies are moremodest in longitudinal studies after statistical control forassociations between cannabis use and other pre-existingcharacteristics that independently predict these adverseoutcomes.
34
A consistent finding in the USA has been the regularsequence of initiation into drug use in which cannabisuse has typically preceded involvement with “harder”illicit drugs such as stimulants and opioids.
5,33,35
Theinterpretation of this sequence remains controversial.
SEMINAR THELANCET • Vol 352 • November 14, 1998
1613
Summary of adverse effects of cannabis
Acute effects
Anxiety and panic, especially in naïve users.
Impaired attention, memory, and psychomotor performance whileintoxicated.
Possibly an increased risk of accident if a person drives a motorvehicle while intoxicated with cannabis, especially if cannabis isused with alcohol.
Increased risk of psychotic symptoms among those who arevulnerable because of personal or family history of psychosis.
Chronic effects (uncertain but most probable)
Chronic bronchitis and histopathological changes that may beprecursors to the developmentof malignant disease.
A cannabis dependence syndrome characterised by an inability toabstain from or to control cannabis use.
Subtle impairments of attention and memory that persist whilethe user remains chronically intoxicated, and that may or maynot be reversible after prolonged abstinence.
Possible adverse effects (to be confirmed)
Increased risk of cancers of the oral cavity, pharynx, andoesophagus; leukaemia among offspring exposed in utero.
Impaired educational attainment in adolescents andunderachievement in adults in occupations requiring high-levelcognitive skills.
Groups at higher risk of experiencing these adverse effects
Adolescents with a history of poor school performance, whoinitiate cannabis use in the early teens, are at increased risk of using other illicit drugs and of becoming dependent on cannabis.
Women who continue to smoke cannabis during pregnancy mayincrease their risk of having a low-birthweight baby.
People with asthma, bronchitis, emphysema, schizophrenia, andalcohol and other drug dependence, whose illnesses may beexacerbated by cannabis use.

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PRMurphy added this note
Within the Weed Belt Update: "Evidence grows that marijuana use can cause acute psychosis, bring forward in time a first schizophrenia episode, and worsen the prognosis of patients with psychotic disorders." ie; AZ Shooter Jared Loughner.
PRMurphy added this note
Based on these studies, if you are a diagnosed schizophrenic, you should NOT be using marijuana or anything containing THC and you should seek immediate mental health assistance.
PRMurphy added this note
RE: AZ Shooter Loughner; There is significant evidence to suggest this man, a diagnosed schizophrenic, broke with reality because of his heavy marijuana usage, which Sarah Palin, Rush, Hannity et al NEVER suggested.
PRMurphy added this note
There is an association between cannabis use and schizophrenia. A prospective study of 50 000 Swedish conscripts45 found a dose-response relation between the frequency of cannabis use by age 18 and the risk of a diagnosis of schizophrenia over the subsequent 15 years. A plausible explanation is that cannabis use can exacerbate the symptoms of schizophrenia,2,46 and there is prospective evidence th
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