Can Cannabis Cure Cancer? We just don't know yet, says Manuel Guzmán

Can cannabis cure cancer? That’s the million dollar question.

Every day there’s another anecdotal report going viral with someone claiming to be cancer free thanks to cannabis.

And yet in oncology, the plant’s use is at best classified as palliative, with THC proving effective for lessening the feelings of nausea from chemotherapy, as well as easing the pain commonly experienced by cancer patients.

Despite hundreds of published papers suggesting that cannabinoids, the active compounds within cannabis may have an anticancer action, the mainstream medical world remain unconvinced.

Is it some big conspiracy as suggested in some quarters? Or simply that as yet, there isn’t sufficient scientific proof?

I wanted to find out how much scientists really know. And who better to speak to than Dr Manuel Guzmán, the Molecular Biologist responsible for what is until now, the only clinical trial using cannabis as a cancer treatment in its own right.

THC – it doesn’t just get you high

But first, let’s get to grips with some of the key players in this piece. When talking about medicinal cannabis, the most commonly mentioned therapeutic compounds are THC (Tetrahydrocannabinol) and CBD (Cannabidiol).

THC, first synthesized in 1964 in Israel by Dr. Raphael Mechoulam, is the most cited cannabinoid and the one used in the clinical trial conducted by Guzmán, but more on that later.

With a psychoactive effect when exposed to heat, it is commonly associated with getting high, although therapeutically it is much more than that. Along with the body’s own endocannabinoid anandamide, THC activates the CB1 receptor mostly found in the central nervous system, thus creating feelings of relaxation and euphoria as well as having anti-inflammatory and pain-relieving effects.

THC could cause cancer cell death

Crucially, the effect of THC on cancer cells, in particular planned cell death or apoptosis, could move the use of medicinal cannabis in cancer treatment to a whole new level.

Cell death is part of life. It can be unplanned through infection, poisoning, overheating or lack of oxygen. Or it can be programmed – a carefully executed cell death, a process that is encoded in the human genome as well as other in organisms.

But in the case of cancer, this apoptosis or programmed cell death no longer functions as it should and there is an uncontrolled growth of certain cells in the body. For a long time researchers have seen the potential of being able to trigger cell death in cancer cells, while keeping healthy cells intact.

This could be where THC comes to the fore.

Key to the process of programmed cell death is a signalling metabolite called Ceramide. If Ceramide levels are high, cell death is imminent, whereas if they are low, apoptosis is less likely.

According to a study carried out in 2009 on mice and human cancer cells, when THC connects to either the CB1 or CB2 receptor sites on a cancer cell, it increases the manufacturing of ceramide, which increases the possibility of cell death. However, non-cancerous cells are not affected, as when THC is introduced, they do not produce ceramide.

In effect, higher levels of ceramide through the introduction of THC, kill the cancer cell’s energy source as well as disrupting their digestive system that provides nutrients for all cell functions. All of which serve to trigger the cancer cell’s suicide, while leaving healthy cells untouched.

But what about CBD?

Compared with THC, much less is known about CBD, which makes it more challenging to understand.

Dr Guzman explains: ‘It’s very likely that the action of the CBD is not explainable by a single lock and key hypothesis as in the case of THC. It’s more complex because it seems that CBD has a low affinity for binding to different proteins, but it also seems that there are many proteins that can interact with CBD’.

He goes on: ‘It seems when you take CBD that nothing happens; I mean it doesn’t get you high. It doesn’t do anything really strong on the body, but it seems that it controls a huge sum of the endogenous (originating from within the body) processes. It’s not that a single molecule binds to a single receptor producing a single effect that can be measured. My belief is that CBD acts very subtly on different levels’.

None the less, scientists have found that when CBD pairs with the cancer cell’s CB2 receptor, it stimulates what is known as the Caspase Cascade, a process involved in the killing of cancer cells.

And in another study carried on aggressive breast cancer cells in mice, this pairing between CBD and the CB2 receptor was also found to bring about a shutting down of the Id-1 gene, the gene that allows metastatic lesions to form. Encouraged by the results, researchers suggested that ‘CBD represents the first nontoxic exogenous (originating from outside the organism) agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness’.

A further potential anti-cancer mechanism of CBD is its ability to prevent new blood cells from growing into tumours – a process called angiogenesis.  In a study published in the British Journal of Pharmacology, CBD was found to inhibit angiogenesis due to various mechanisms supporting ‘the hypothesis that CBD has potential as an effective agent in cancer therapy’.

However, for Dr Guzmán, ‘the most remarkable action of cannabis on cancer is primarily that it kills cancer cells. As the tumour has less cells, so it needs less blood vessels to sustain itself. So it would seem that angiogenesis is something that is really secondary to apoptosis’.

First ever clinical trial tests cannabis on cancer patients

Manuel Guzmán is a trailblazer in cannabis research having conducted the only published clinical trial using a cannabinoid to treat cancer. In a phase one clinical trial, nine patients suffering from glioblastoma, an aggressive form of brain tumour, were administered THC through a catheter directly into the tumour.

With a common prognosis of little more than 24 weeks, researchers were encouraged that two patients were alive one year later (although they have both since died). They also noted that THC was at least safe and did “not facilitate tumour growth nor decrease patient survival.”

Guzmán says: ‘The significance is little in clinical terms. But, it provided some hints towards possible anti-tumoral action of THC in certain patients. It’s not the case that the patients got their tumour eradicated but it seemed on biological grounds from measuring markers in the tumour biopsies, that cannabis or THC in this case, had been effective in decreasing the malignancy and the growth of the tumours, at least in some of the patients’.

A further clinical trial with glioblastoma patients has taken place carried out by GW Pharma using the drug Sativex in which patients were given the THC/CBD drug alongside temozolomide, a form of chemo given to patients. The patients taking the combination treatment had an 83% one year survival rate, compared to 53% for patients who were just undergoing chemotherapy alone.

Lack of sufficient clinical trials

But still, in relative terms clinical trials for the use of cannabis in cancer treatment are few and far between. The proximity to death of many cancer patients makes traditional testing difficult.

‘It’s true,’ says Guzmán, ‘that in orthodox pharmacology, we always require complex trials that are double blind and randomised, but I think ethically speaking (in cancer) short cuts should be allowed’. He also points out that companies are also less inclined to invest in trials for compounds like cannabinoids that can’t be patented.

This lack of clinical trials is the main criticism levelled by cancer charities like Cancer Research UK who say, ‘virtually all the scientific research investigating whether cannabinoids can treat cancer has been done using cancer cells grown in the lab or animal models. It’s important to be cautious when extrapolating these results up to real live patients, who tend to be a lot more complex than a Petri dish or a mouse’.

Of mice and not men

Something that Guzmán tends to agree with. ‘One has to consider when one cures cancer in a mouse, it’s not really cancer, it’s a model of cancer which has only part of the characteristics of human cancer. So the gap between curing the cancer in a mouse and curing the cancer in a human is enormously huge’.

He goes on, ‘even in a sophisticated cancer model in mice – in the end mice are mice. It’s not just a 25 gram human. Mice have a much simpler biology than ours and mice are much stronger than we are. They have a strong capacity for tissue regeneration, they have a very strong immune system, much more than ours.

‘In mice there are hundreds of molecules that can cure cancer, but there are very few molecules that can do that in humans.’

Cautiously hopeful

But despite these words of caution, Guzmán remains positive that the results of this first clinical trial on humans did indeed have important significance.

‘In general terms, if nothing else it served to open the minds of oncologists and tell them ,“well, these trials show that maybe, in some instances cannabinoids could help manage cancer”. It’s a very first step, but it’s better than nothing.’

Dr Manuel Guzmán is Professor at the Department of Biochemistry and Molecular Biology at Complutense University in Madrid, Spain. He coordinates the Cannabinoid Signalling Group.

Article originally published on Endoca Foundation

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