Cannabis and tobacco smoke are not equally carcinogenic

[Sequoiacrone]

Harm Reduct J. 2005; 2: 21.
Published online 2005 October 18. doi: 10.1186/1477-7517-2-21.

PMCID: PMC1277837
Copyright © 2005 Melamede; licensee BioMed Central Ltd.

Cannabis and tobacco smoke are not equally carcinogenic
Robert Melamede1,2 1Biology Department, 1420 Austin Bluffs Parkway, University of Colorado, Colorado Springs, 80918, USA
2Bioenergetics Institute, 1420 Austin Bluffs Parkway, University of Colorado, Colorado Springs, 80918, USA

Corresponding author.
Robert Melamede: rmelamed@uccs.edu
Received November 30, 2004; Accepted October 18, 2005.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.


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Abstract
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Abstract
More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer. Keywords: marijuana, tobacco, cancer, smoke, cannabinoids, carcinogens, nicotine

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Abstract
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References


Tobacco has dramatic negative consequences for those who smoke it. In addition to its high addiction potential [1], tobacco is causally associated with over 400,000 deaths yearly in the United States, and has a significant negative effect on health in general [2]. More specifically, over 140,000 lung-related deaths in 2001 were attributed to tobacco smoke [3]. Comparable consequences would naturally be expected from cannabis smoking since the burning of plant material in the form of cigarettes generates a large variety of compounds that possess numerous biological activities [4].
While cannabis smoke has been implicated in respiratory dysfunction, including the conversion of respiratory cells to what appears to be a pre-cancerous state [5], it has not been causally linked with tobacco related cancers [6] such as lung, colon or rectal cancers. Recently, Hashibe et al [7] carried out an epidemiological analysis of marijuana smoking and cancer. A connection between marijuana smoking and lung or colorectal cancer was not observed. These conclusions are reinforced by the recent work of Tashkin and coworkers [8] who were unable to demonstrate a cannabis smoke and lung cancer link, despite clearly demonstrating cannabis smoke-induced cellular damage.
Furthermore, compounds found in cannabis have been shown to kill numerous cancer types including: lung cancer [9], breast and prostate [10], leukemia and lymphoma [11], glioma [12], skin cancer [13], and pheochromocytoma [14]. The effects of cannabinoids are complex and sometimes contradicting, often exhibiting biphasic responses. For example, in contrast to the tumor killing properties mentioned above, low doses of THC may stimulate the growth of lung cancer cells in vitro [15].
The genotoxic effects of partially oxidized hydrocarbons created by burning either cannabis or tobacco have been widely examined as the likely source of genetic changes that lead to the carcinogenic state [16]. As a result, the medical potential of cannabis has been obscured by the potential negative impact of using a smoked medicine [17]. Those who deny the validity of "medical marijuana," cite that marijuana smoke contains four fold more tars than does tobacco smoke [18]. Nevertheless, smoking is often the preferred route of intake by medical cannabis users because rapid action allows self-titration [19]. Are the biological consequences of smoking cannabis and tobacco similar?
Smoke from tobacco and cannabis contains many of the same carcinogens and tumor promoters [20,21]. However, cannabis and tobacco have additional pharmacological activities, both receptor-dependent and independent, that result in different biological endpoints. Polycyclic aromatic hydrocarbons found in smoke are pro-carcinogens that are converted to carcinogens by the enzymatic activity of the cytochrome P4501A1 oxidase protein (CYP1A1 gene product). Benzo [a] pyrene is converted to its carcinogenic metabolite diol epoxide, which binds to specific hyper-mutable nucleotide sequences in the K-ras oncogene and p53 tumor suppressor [22]. Recent work by Roth et al. demonstrates that THC treatment of murine hepatoma cells caused a dose dependent increase in CYP1A1 gene transcription, while at the same time directly inhibiting the enzymatic activity of the gene product [23]. Thus, despite potentially higher levels of polycyclic aromatic hydrocarbons found in cannabis smoke compared to tobacco smoke (dependent on what part of the plant is smoked), the THC present in cannabis smoke should exert a protective effect against pro-carcinogens that require activation. In contrast, nicotine activates some CYP1A1 activities, thus potentially increasing the carcinogenic effects of tobacco smoke [24].
It is worth noting that cytochrome P4501A1 oxidase has numerous substrates including biologically active lipid metabolites such as arachidonic acid, and eicosinoids [25]. These molecules are components of metabolic pathways that are interwoven with the synthesis and degradation of endocannabinoids such as arachidonylethanolamine (anandamide) [26]. Hence, the inhibition of cytochrome P4501A1 oxidase by THC is likely to have multiple biological effects such as possibly enhancing cannabinoid activities by decreasing their catabolism.
The need to better understand the biological consequences of tobacco compared to cannabis smoke has been underscored by recent studies that demonstrate a unique role for nicotine in the pathogenesis of lung cancer [27]. In order to appreciate potential biological differences between tobacco and cannabis smoke, the molecular basis of signal transduction must be considered with respect to the life and death of cells. Evolution has provided cells with biochemical feedback loops, checkpoints that monitor genetic integrity and the overall state of the cell. Under conditions of sufficient cellular damage, apoptotic cell death is induced [28]. While a variety of different biochemical states are consistent with a cell either living or dying, constant communication between a cell and its environment is critical for survival of the cell and ultimately the organism.
Cells communicate with each other via specific cell surface receptors. When bound with their appropriate ligand, the receptors initiate signaling cascades that alter cellular biochemistry [29]. THC found in cannabis [30] and nicotine found in tobacco [31] both have specific receptors by which their corresponding ligands modulate cellular functions. Interestingly, both cannabinoid [32] and nicotine receptors [27] are coupled to the AKT (PKB) signaling pathway. Activation of either receptor type can induce an anti-apoptotic state that prevents cell death. However, it is the context in which the AKT pathway is activated that determines whether an organism benefits or is harmed by this anti-apoptotic activity.
Nicotine receptors are widely distributed and are found in the epithelial cells lining respiratory passages. Cannabinoid receptors are also widely distributed, but have not been reported in respiratory epithelial cells. The differential expression of receptors may account for the apparent difference in carcinogenic activity that results from smoking tobacco compared to cannabis. Both types of smoke contain a complex mixture of compounds, some of which are carcinogenic. They both contain hot gasses and irritating particulate matter (tars). However, the anti-apoptotic response that results from the stimulation of the nicotine receptors, under mutagenic conditions, creates a worst-case scenario. The very cells that have accumulated sufficient genetic damage to normally initiate the apoptotic cascade are prevented from going down this suicidal path [33] even though it would be best for the organism as a whole. In contrast, when the AKT pathway is activated in the brain after head injury [34] or stroke, [35] cannabinoids protect against cell death to the organism's benefit. Likewise, nicotine can also activate the AKT pathway in the brain in a beneficial manner. For example, activation of the nicotine receptors, as is also true of cannabinoid receptors [36], can prevent the brain cell death that results from exposure to beta amyloid protein [37] as occurs in Alzheimer's disease.
The impact of receptor and downstream activation is complicated. Both nicotine and cannabinoids have been shown to effect angiogenesis in a receptor-mediated manner [13]. However, nicotine and tobacco have opposite effects on angiogenesis. Nicotine promotes neo-vacularization along with associated tumor growth, atheroma, up-regulation of VEGF, and cell migration [38]. In contrast, cannabinoids promote tumor regression in rodents and inhibit pro-angiogenic factors [39]. In fact, clinical trials to treat human glioma with THC have resulted in decreased levels of VEGF [40].
The signal transduction pathway described above represents one means by which the carcinogenic affects of tobacco are amplified in a contrasting manner to what occurs with cannabis. The immunological effects resulting from smoking tobacco or cannabis are also distinctive and result in opposite end-points. Again, the carcinogenic potential of smoke is increased by tobacco, whereas it is uniquely reduced by the specific immune regulatory activity of cannabinoids in cannabis smoke. The introduction of hot gaseous material containing both carcinogens and particulate material into the respiratory passages produces pro-inflammatory immune responses [41]. The inflammatory state is a double-edged sword that can serve to protect or kill an organism. A functional characteristic of the pro-inflammatory state is the production of free radicals [42]. These reactive chemical species are essential armaments in the body's defense against various pathogens, in particular against intracellular parasites and bacteria. Free radicals are thought to be contributing etiological agents behind a number of pathological states [43] including cardiovascular and neuro-degenerative diseases [44], cancers, and aging in general [45]. Endocannabinoids are specific immunological homeostatic modulators when acting on "peripheral" CB2 receptors [30]. Both endo- and exo-cannabinoids push the immune system towards the relatively anti-inflammatory Th2 cytokine profile [46]. Thus, cannabinoids inhaled in cannabis smoke physiologically reduce the potential amplification of carcinogens in smoke that results from biologically produced free radicals. This response is not induced by tobacco smoke.
In conclusion, while both tobacco and cannabis smoke have similar properties chemically, their pharmacological activities differ greatly. Components of cannabis smoke minimize some carcinogenic pathways whereas tobacco smoke enhances some. Both types of smoke contain carcinogens and particulate matter that promotes inflammatory immune responses that may enhance the carcinogenic effects of the smoke. However, cannabis typically down-regulates immunologically-generated free radical production by promoting a Th2 immune cytokine profile. Furthermore, THC inhibits the enzyme necessary to activate some of the carcinogens found in smoke. In contrast, tobacco smoke increases the likelihood of carcinogenesis by overcoming normal cellular checkpoint protective mechanisms through the activity of respiratory epithelial cell nicotine receptors. Cannabinoids receptors have not been reported in respiratory epithelial cells (in skin they prevent cancer), and hence the DNA damage checkpoint mechanism should remain intact after prolonged cannabis exposure. Furthermore, nicotine promotes tumor angiogenesis whereas cannabis inhibits it. It is possible that as the cannabis-consuming population ages, the long-term consequences of smoking cannabis may become more similar to what is observed with tobacco. However, current knowledge does not suggest that cannabis smoke will have a carcinogenic potential comparable to that resulting from exposure to tobacco smoke.
It should be noted that with the development of vaporizers, that use the respiratory route for the delivery of carcinogen-free cannabis vapors, the carcinogenic potential of smoked cannabis has been largely eliminated [47,48].

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Competing interests
The author(s) declare that they have no competing interests.

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Abstract
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References

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[Sequoiacrone]

Why Doesn't Smoking Marijuana Cause Cancer?

Posting Date: 11/25/1999

Original broadcast date: July 15, 1999
Haroon: There's such a big to-do about smoking and cancer, but people smoke marijuana and call that medicinal.
I was told that the heat from the smoke causes cancer among tobacco smokers. But then wouldn't smoking marijuana cause cancer, too?
Dr. Dean: Haroon, this is the big question about smoking. You'd think we'd know by now what part of it causes cancer, but we don't. Some of the theories are tars, polonium, and, as you mentioned, the burning process....
See the whole article here:
http://www.healthcentral.com/drdean/408/14275.html


I can't resist this clip from the article cited here.

One of the main reasons we can't pinpoint what part of smoking causes cancer is that cigarette companies have a big secret. An incredible loophole in the law allows them not to disclose about 500 of the ingredients in cigarettes. Maybe the burning of one of those ingredients causes lung cancer. But we can't test it, because we don't know what it is.

[Sequoiacrone]

--------------------------------------------------------
IACM-Bulletin of 23 November 2008
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We would like to create a forum for discussions and questions on
the French site of the IACM website. Such forums are already
present on the German and the Spanish site. Two patients would
like to oversee the forum, but they need support by a doctor or
scientist with knowledge on the pharmacology and toxicology of
cannabis. Interested French speaking doctors or scientists are
invited to write to info@cannabis-med.org.

* Science: Why cannabis smokers may have a lower cancer risk
than tobacco smokers

1.

Science: Why cannabis smokers may have a lower cancer risk
than tobacco smokers

Eleven scientists from the USA and Taiwan summarized data
from basic research and a re-evaluation of an epidemiological
study by Sidney and colleagues from 1997. Their investigation
indicates that cannabis smoke may not increase or even decrease
the incidence of cancers associated with tobacco smoke. While
cannabis smoke contains higher levels of carcinogenic polycyclic
aromatic hydrocarbons (PAH) than in tobacco smoke, this may
not mean that cannabis smokers are at a higher cancer risk than
tobacco smokers, since the level of PAHs is less important than
the influence of substances on PAH activation by certain
enzymes in the liver. "Not surprisingly, spiking tobacco tar with
delta-9-THC markedly reduced carcinogenic activity" in
experiments with cancer cells, scientists wrote in an article for the
Journal of Psychoactive Drugs.

It is known that cannabis smoking causes precursors of cancer,
which are also observed in tobacco smokers. However, studies
show that these precursors "may have little, if any predictive
value" and these lesions are "generally reversible and often
regress spontaneously." In studies with monkeys "prolonged
exposure to marijuana smoke failed to produce any carcinogenic
effects."

In the cohort study by Sidney et al. (1997) with about 65,000
subjects tobacco smokers had a significantly higher risk to develop
lung cancer than cannabis smokers after a mean observation
period of 8.6 years. In addition, cannabis smokers had a
significantly lower lung cancer risk than subjects, who did not
smoke cannabis. In reply to the argument, Sidney and colleagues
did not follow the participants of their study long enough to find an
increased incidence of cancers in the cannabis group, they noted
that "surprising enough, the follow-up period was sufficient to
observe 179 cases of TRC [tobacco related cancers] (including
lung) among TS [tobacco smokers]." If the cancer risk of tobacco
smokers equals that of non-smokers, then 130 cases would be
expected among tobacco smokers. In contrast, only three cases of
tobacco related cancers were observed in cannabis smokers. If
the incidence of tobacco related cancers in cannabis smokers
equals that of non-smokers, "then 16 cases would be expected in
MS [marijuana smokers]."

(Source: Chen AL, Chen TJ, Braverman ER, Acuri V, Kemer M,
Varshavskiy M, Braverman D, Downs WB, Blum SH, Cassel K,
Blum K. Hypothesizing that marijuana smokers are at a
significantly lower risk of carcinogenicity relative to tobacco-non-
marijuana smokers: evidenced based on statistical reevaluation of
current literature. J Psychoactive Drugs 2008;40(3):263-72.)

2.

News in brief

***USA: New Mexico
Since medicinal cannabis was legalized in New Mexico in 2007,
there are about 200 medical cannabis users in the state, according
to the Drug Policy Alliance. However, patients have no place to
legally purchase the drug. (Source: Daily Lobo of 13 November
2008)

***Science: Tobacco and THC
According to research at the University of Leiden, the
Netherlands, mixing cannabis with tobacco increased the amount
of THC inhaled per gram of cannabis from a mean of 33 mg/g for
a cigarette only containing cannabis to 59 mg/g for a cigarette
containing 25 per cent cannabis and 75 per cent tobacco. (Source:
Van der Kooy F, et al. Inhal Toxicol. 2008 Oct 14:1. [Electronic
publication ahead of print])

***Czech Republic: Cannabis laws
The possession of a small amount of cannabis for personal use
would be punished far less strictly than that of other drugs,
according to a change of the law by the lower house of parliament
on 11 November. While the production and sale of drugs can be
punished with five to 15 years in prison, if people have a small
amount of cannabis on them it is only an offence, under the new
law. It is yet to be discussed by the upper house and signed by the
president into law. (Source: Ceske noviny of 11 November 2008)

***The Netherlands: Mayors
A majority of Dutch mayors (54 out of 88), who have a coffee
shop in their city, support the legalisation of the entire cannabis
production chain. They want to end the frontdoor-backdoor
problem, where sales of cannabis is legal but growing is not.
(Source: Psychonaut.com of 19 November 2008)

***Science: Psychosis
According to British researchers the use of cannabis causes
increased experiences of delusions and hallucinations in individuals
prone to psychosis. Their findings suggest that an individual's
response to acute cannabis consumption may be a marker of
occurrence of harmful psychic effects of cannabis. (Source:
Mason O, et al. Psychol Med. 2008 Nov 19:1-6. [Electronic
publication ahead of print])

***Science: Cannabis dependence
A study conducted in the USA with 1.923 subjects shows that
certain variations of the DNA sequence of the gene for the
cannabinoid-1 receptor may be associated with an increased risk
for cannabis dependence. (Source: Agrawal A, et al. Am J Med
Genet B Neuropsychiatr Genet. 2008 Nov 14. [Electronic
publication ahead of print])

***Science: Schizophrenia
According to research at the Psychiatric University Hospital
Zurich, Switzerland, on the reasons for cannabis use patients with
schizophrenia more often than healthy controls stated that they
consumed cannabis to fight boredom and to ease social contacts.
(Source: Schaub M, et al. Aust N Z J Psychiatry
2008;42(12):1060-5.)

***Science: Pain
Scientists from the University of Bonn, Germany, demonstrated
that the CB2 receptor in cells of the immune system is involved in
the development of neuropathic pain. The CB2 receptor was
important for the modulation of the activation of glia cells in
response to nerve injury. (Source: Racz I, et al. J Neurosci
2008;28(46):12125-35.)

***Science: Food intake
Animal research shows that CB2 receptor ligands, i.e. substances
that bind to the CB2 receptor, may play a role in food and alcohol
consumption. (Source: Onaivi ES, et al. Ann N Y Acad Sci
2008;1139:426-33.)

***UK: Poll on illegal drugs
According to a poll conducted for the Observer and the Guardian
newspapers 27 per cent of UK adults have taken illegal drugs and
87 per cent of these have taken cannabis. 32 per cent believe that
drug laws in the UK are too liberal, 50 per cent think that they are
about right and 18 per cent believe that they are not liberal
enough. 27 per cent of responders said that certain drugs should
be legalized or decriminalized. A sample of 1,008 UK adults aged
16 years or older were interviewed by ICM Research in October
2008. (Source: The Observer of 16 November 2008)

NEW BOOK
* Gieringer D, Rosenthal E, Carter GT. Marijuana Medical
Handbook. Quick Trading Co. ISBN: 978-093255186-3.

3.

ONE YEAR AGO:
- Science: Cannabis improved neuropathic pain in clinical study
- Science: Cannabidiol may be helpful in reducing the
aggressiveness of breast cancer cells

TWO YEARS AGO:
- The Netherlands: The governments of Canada, Germany and
Italy are interested in medical cannabis from the Netherlands
- USA: Tentative ruling in support of the Californian medical
cannabis law
- Science: Evaluation of herbal cannabis by medical users in
controlled study
- Science: Why cannabis use impairs memory and may help
against epilepsy

(More at the IACM-Bulletin archives: http://www.cannabis-
med.org/)

International Association for Cannabis as Medicine (IACM)
Am Mildenweg 6
D-59602 Ruethen
Germany
Phone: +49 (0)2952-9708571
Fax: +49 (0)2952-902651
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The articles of the IACM-Bulletin can be printed, translated and
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original work is properly cited. The source of the IACM-Bulletin
is "IACM, www.cannabis-med.org".

[Sequoiacrone]

Inhaling cannabis without the smoke 12 May 2007 Vapourising cannabis leaves instead of burning them can release the drug's active ingredient just as effectively — while avoiding the harmful toxins inhaled through smoking the drug, according to a pilot study.

The result could be good news for those who choose to use marijuana medicinally.

The potential benefits of marijuana include pain relief for multiple-sclerosis sufferers, a treatment for glaucoma, as an appetite stimulant for AIDS patients and an anti-nausea agent for people on chemotherapy. But smoking isn't a good method of drug delivery because the harmful effects — such as lung cancer and heart disease — outweigh the likely merits of marijuana for all but terminal cases.

Rather than smoking, some use the leaves to make tea or cakes for consumption. But this means that the active agents are metabolised by the liver rather than entering the bloodstream unaltered. Others have focused on extracting active ingredients such as tetrahydrocannabinol (THC) and delivering them alone in a pill or oral spray. However, many think that the isolated ingredients are not as effective as the whole plant, and it is more difficult to customise the dose for each individual with a pill.

Hot stuff

Donald Abrams of the University of California, San Francisco, and his team decided to investigate the benefits of the 'Volcano', a commercially available vaporiser. The device heats marijuana leaves to a temperature between 180 and 200 °C so that THC is released from oils on the surface of the leaf but no actual combustion takes place.

Previous studies have shown that harmful toxins released through smoking cannabis such as carbon monoxide, benzene and a host of compounds known as polycyclic aromatic hydrocarbons (many of which are known carcinogens) are not produced by such devices.

Abrams' study is the first to compare the effects of smoking and vaporising cannabis on human subjects. "We were able to deliver more-or-less equivalent amounts of THC into the bloodstream," he says. The main difference between the two delivery methods was that THC seemed to be absorbed into the bloodstream faster when using the vaporiser. "The pharmacological and physiological effects were comparable," he says, although a larger study would be needed to prove that they are biologically equivalent.

Slow burn

The first studies to highlight the advantages of using vaporisers for cannabis were published more than five years ago, but the pace of research has been slow, partly because there is only one source of research-approved marijuana in the United States — the National Institute on Drug Abuse (NIDA) — which critics accuse of dictating research along a political agenda. A legal ruling this February recommended that the US Drug Enforcement Administration (DEA) end NIDA's monopoly on the production of marijuana for research approved by the US Food and Drug Administration and by the DEA.

Laura Bell of the Multiple Sclerosis Society in the UK says that her society supports cannabinoid research for people with multiple sclerosis. "Smoking cannabis results in exposure to many toxic chemicals," she says. "We welcome research into better and safer delivery methods."

Cannabis leaf is not the only substrate suited to a vaporiser. Other herbal preparations, such as eucalyptus and chamomile can also be used, or any plant with medicinal properties in the volatile compounds of its leaves.

Source: news@nature.com ©2007 Nature Publishing Group (12/05/07)

[Sequoiacrone]

SMOKED CANNABIS' EFFECT ON LUNGS

Does regular marijuana smoking cause COPD, Emphysema and/or Lung
Cancer? In part 1, Donald Tashkin, MD examines risk of Chronic
Obstructive Pulmonary Disease.

http://www.youtube.com/watch?v=PXKhHv5VuEI

[Sequoiacrone]

http://www.youtube.com/watch?v=lffUB...eature=related

[Sequoiacrone]

http://www.youtube.com/watch?v=U6xxi...eature=related