May 2010: Increased Pulmonary Function with Switch to Vaporized Cannabis. (SUNY; Albany, New York)

First some background: When solid particles are burned, they release a variety of molecules as smoke due to the addition of energy in the form of fire. With this addition of energy, a series of chemical reactions occur that release liquid particles and gases that often are of different composition than the original compound. Most often, when an organic compound, such as cannabis, is burned, it emits gases such as carbon monoxide and hydrogen cyanide that may be harmful to the user. Aside from the stigma attached to the name, the potential harmful effects of smoke are one of the main reasons why marijuana is not widely accepted in the medical community. However, there are other ways of administration besides inhaling smoke, such oral or inhaling vapor. Vaporizers heat the cannabis to around 400⁰ F without burning the plant material, reaching the boiling point of most cannabinoids and releasing them in a mist, with not enough heat applied to release other, more harmful compounds.

The new information: In this experiment, twenty frequent cannabis smokers were used to determine the differential effects of inhaling smoke or vapor. The twenty smokers had previously reported at least two respiratory side-effects and were asked to self-report their severity of symptoms. Additionally, their forced expiratory volume (FEV1) and forced vital capacity (FVC) were measured. FEV1 refers to the maximum volume of air that can be exhaled in 1 second, and FVC refers to the total volume of air that the lung can hold. The smokers were then switched to using vaporizers for one month and the measurements were repeated. Initially, average self-reported symptoms were graded to be 26.1, FVC was 4.54L, and FEV1 was 3.22L; after 1 month of vaporizer use, average self-reported symptoms dropped to 6.92, FVC was 4.76L, and FEV1 was 3.6L. The study used 8 males and 4 females (8 of the subjects ended up smoking during the 1 month period) with an average age of 20 years. For these figures, the normal values for FVC and FEV1 should be 4.89 and 4.06L respectively. It should also be noted that approximately a quarter (3) of the subjects also reported tobacco use.

What this means: The results of this experiment indicate that utilizing vaporized cannabis instead of smoke may improve respiratory side-effects and overall pulmonary function. Additionally, this study only represented the improvement after one month of switching to vaporized cannabis, and improvements may increase with an increased time interval. Therefore, utilizing cannabis in vaporized form is significantly safer than smoking it.

Earleywine, M. and Van Dam, N.T. “Pulmonary Function in Cannabis Users: Support for a Clinical Trial of the Vaporizer.” The International Journal on Drug Policy. (2010): preprint.

May 2010: Cannabinoids do not cause oxidative stress as previously thought. (Universidade do Porto; Porto, Portugal)

First some background: In order for human beings to survive, they must consume oxygen. This oxygen consumption drives the most basic of metabolic processes, allowing us to efficiently utilize carbohydrates, proteins, and fats as cellular sources of energy. The final conversion of these molecules to energy occurs within a cellular organelle known as the mitochondria. Within the mitochondria, oxygen is reduced and coupled with hydrogen to produce water, and a resulting hydrogen gradient drives the formation of ATP (cellular energy). However, this process is slightly inefficient, as some of the reduced oxygen fails to couple with hydrogen and become reactive oxygen species, such as superoxide. These reactive oxygen species may cause damage to a cell’s DNA, RNA, or proteins, but are normally converted by a series of enzymes (e.g. superoxide dismutase) into non-reactive molecules. Oxidative stress occurs when the balance between reactive species formation and conversion are disrupted, causing an accumulation of reactive oxygen species and an increase in cellular damage. Reactive oxygen species may also be formed as a byproduct of several other processes such as drug metabolism by cytochrome P450 enzymes. ∆⁹-Tetrahydrocannabinol (THC) has been previously reported to cause oxidative stress due to an increase in reactive oxygen species formation.¹

The new information: In this experiment, mice were injected with either THC, vehicle (the contents of the THC injection without the actual THC), or nothing. The mice livers were then analyzed for the activity level of enzymes that interact with reactive oxygen species: superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase. Additionally, the biomarkers indicating oxidative stress in the mouse liver were lipid peroxidation, protein carbonylation, and DNA oxidation. The results showed that THC caused no change in the activity levels of all 5 enzymes and no biomarkers for oxidative stress were observed. Additionally, the vehicle actually caused an increase in glutathione peroxidase activity, indicating an increase in levels of hydroperoxides, a type of reactive oxygen species. But in the THC injection, the glutathione peroxidase activity level was normal, indicating that THC actually reduced the level of oxidative stress caused by the vehicle.

What this means: This experiment shows that THC in fact does not cause oxidative stress in the liver, and disproves several theories that have been previously presented. This goes to further dispel some of the notions that cannabinoids are more harmful than beneficial for the patient. Additionally, by opposing the increase in glutathione peroxidase activity caused by the vehicle, THC may in fact be an antioxidant in the liver as it has been shown to be in the brain.² This indicates that cannabinoids may be beneficial in treating other liver diseases besides hepatitis C.

¹Sarafian, T.A., et al. “Oxidative Stress Produced by Marijuana Smoke. An Adverse Effect Enhanced by Cannabinoids.” American Journal of Respiratory Cell and Molecular Biology. 20.6(1999): 1286-93.

²Hampson, A.J., et al. “Cannabidiol and (−)Δ9-Tetrahydrocannabinol are Neuroprotective Antioxidants.” Proceedings of the National Academy of Sciences of the United States of America. 95.14(1998): 8268-73.

Pinto, C.E., et al. “Effect of (-)-Delta(9)-Tetrahydrocannabinoid on the Hepatic Redox State of Mice.” Brazilian Journal of Medical and Biological Research. 43.4(2010): 325-9.

May 2010: Cannabinoids may be used to target brain cancer cells. (University of the Basque Country; Leioa, Spain)

First some background: Brain cancer refers to the uncontrolled growth of cells in the brain, mainly neurons or glial cells. Glial cells refer to brain cells which do not actually conduct the signals that give rise to bodily function, but rather play a supportive role for neurons. When cancer arises from glial cells, such as oligodendrocytes, astrocytes, microglia, and ependyma, the tumor is referred to as a glioma. Malignant gliomas are the most prominent form of life-threatening brain cancer as well as one of the most aggressive forms of cancer known; thus although gliomas are not the most common, they are one of the most deadly cancers. Additionally, unlike lung or colon cancer, there are no known environmental factors that may cause brain cancer besides vinyl chloride or radiation, which the average person is not readily exposed to; and diagnosing brain cancer involves more expensive imaging techniques. These factors combined make gliomas one of the hardest forms of cancer to battle.

The new information: This experiment aimed to elucidate changes in cannabinoid receptor expression of gliomas. It was conducted by introducing antibodies raised against the receptors to human glial tumors and measuring the rate and levels at which the antibodies bound both cannabinoid receptor 1 and 2 (CB1 and CB2). It was found that in glioblastoma multiforme (the typical glioma), levels of CB1 were decreased by 43% and levels of CB2 were increased by 765% compared to a sample of normal, healthy brain tissue.

What this means: By altering levels of cannabinoid receptors, the brain cancer cells now differentiate themselves in terms of their response to cannabinoids. It has been widely documented that cannabinoids may induce cell apoptosis via CB2 receptors, and thus this astounding increase in CB2 receptor expression by gliomas make them far more susceptible to programmed cell death than other brain cells. Thus, levels of cannabinoids that would be safe for normal brain tissue would cause death in brain cancer cells. Therefore, cannabis may have potential therapeutic effects for those diagnosed with brain cancer, and more specifically, glioblastoma multiforme (GBM).

De Jesús, M.L., et al. “Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.” Neurochemistry International. 56.6-7(2010): 829-33.

June 2010: Cannabinoids inhibit a group of cancer-causing enzymes. (Hokuriku University; Kanazawa, Japan)

Note: June refers to the publication date

First some background: The human body contains an expansive number of enzymes, proteins which increase the rate of chemical reactions in our bodies. These enzymes typically facilitate the various molecular metabolic processes that are occurring at any given second within our cells, but some of their products and/or byproducts can be harmful, even carcinogenic (cause cancer). Perhaps the largest group of enzymes in our bodies is the cytochrome P450 (CYP) family, which catalyze the monooxidation (addition of one oxygen) of various organic molecules. One of the main functions of this enzyme family is the metabolism of drugs in the liver. However, some subfamilies, such as the CYP1 subfamily (enzymes CYP1A1, CYP1A2, CYP1B1), also induce the formation of carcinogenic compounds from polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbons are common constituents of smoke, especially cigarette smoke, and are known as procarcinogens. The label procarcinogen indicates that the molecule in and of itself will not cause cancer, but can be induced to cause cancer when altered by a metabolic process.

The new information: This experiment tested the effects of three cannabinoids found in marijuana on the catalytic effects of CYP1 enzymes. The three cannabinoids used were delta(9)-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; it was found that all three cannabinoids inhibited all three CYP1 enzymes to some degree, with THC being the least potent inhibitor, cannabidiol inhibiting CYP1A1 most effectively, and cannabinol inhibiting CYP1A2 and CYP1B1 most effectively. Additionally, it was shown that all three cannabinoids were competitive inhibitors, meaning that at higher concentrations/potencies of other substrates for the CYP1 enzymes, the cannabinoids were displaced.

What this means: By illustrating that three of the major cannabinoids found in marijuana can cause potent inhibition of all three enzymes in the CYP1 subfamily, marijuana may prevent certain forms of cancer. Polycyclic aromatic hydrocarbons are common components in environmental pollution, and are usually inhaled, resulting in lung cancer. By inhibiting the enzyme that converts the procarcinogen into the cancer-causing compound, cannabis may be prophylactically used to prevent one of the main causes of lung cancer. Additionally, because CYP1 enzymes are also involved in drug metabolism, cannabis could be use to augment various pharmaceuticals for maximal effectiveness. In order for a drug to be excreted from the body, it generally first passes through at least two phases of metabolism, with cytochrome P450 enzymes representing one of the major components of the first phase. Thus if a drug is known to be metabolized by one of the CYP1 enzymes and cannabis is co-administered, it would take longer for the drug to be broken down in and removed from our bodies. Therefore, cannabis could extend the half-life of various medications, possibly reducing the cost to patients.

Yamaori, S., et al. “Characterization of Major Phytocannabinoids, Cannabidiol and Cannabinol, as Isoform-selective and Potent Inhibitors of Human CYP1 Enzymes.” Biochemical Pharmacology. 79.11(2010): 1691-8.

March 2010: A novel process by which cannabinoids alleviate pain has been determined molecularly (Medizinische Hochschule Hannover; Hannover, Germany)

First some background: Chronic pain is often a difficult condition to treat and sometimes even diagnose. Originating as a protective mechanism, pain notifies us when an external stimulus may cause us harm or when something internal start to go awry. However, in certain types of chronic pain and what is referred to as neuropathic pain, this once protective mechanism exhibits functional degeneracy, where its function in the human body is not established. What has been well established however, is the process by which we feel this pain. When peripheral cells are damaged, an inflammatory response ensues, leading to the release of chemicals such as bradykinin, histamine, prostanoids, and tachykinins. These chemicals as well as physical pressure and severe temperatures act on dendritic terminals of nociceptive neurons, mostly activating TRP (transient receptor potential) channels. These TRP channels are a family of stimulus-sensitive non-selective cation channels, thus permeable to sodium, calcium, magnesium, and other positively charged ions. Activation of TRP channels causes a signal to be sent along this nociceptive (pain) neuron, whose cell body resides in the dorsal root ganglion. These cell bodies then relay their signal to a different neuron in the spinal cord. This spinal cord neuron, located in the dorsal horn, also receives input from several other neurons, dictating the level of pain felt and are usually inhibitory. It is well documented that cannabinoids can act in a retrograde fashion at these synapses utilizing CB1 (cannabinoid receptor 1) in order to inhibit the signal coming from the primary afferent neuron (the one that originally sensed the pain). Additionally, it has been established that cannabinoids may act at TRP channels directly, desensitizing them to painful stimuli. However, in recent years, it has emerged that cannabinoids may also act on other parts of the pain pathway.

The new information: Although it has been previously noted that cannabinoids act on different parts of the pain pathway, including glycine receptors, the exact molecular mechanism has not been established. The modulatory inhibitory neurons utilize one of two neurotransmitters to decrease the painful signal coming from the primary afferent neuron: GABA (gamma-aminobutyric acid) and glycine. It is known that cannabinoids somehow act on glycine receptors in order to decrease the sensation of pain. This experiment involved mutating the glycine receptor in specific regions to determine how cannabinoids, specifically cannabidiol, interact with the receptor. By mutating an amino acid in the second transmembrane domain from serine (polar) to isoleucine (nonpolar), cannabidiol had no effect on the receptor. However, in absence of the mutation, cannabidiol caused both co-activation and direct activation of the glycine receptor. Co-activation is also referred to as positive allosteric modulation, where the cannabinoid by itself will not activate the receptor, but in presence of glycine (the receptor agonist), there is an increased intracellular response. Additionally, cannabidiol was shown to directly activate this receptor, causing inhibition of the noxious (painful) signal.

What this means: As mentioned in previous entries, THC (∆9-tetrahydrocannabinol) is not the only cannabinoid found in plants of the Cannabis genus. The remaining cannabinoids all have differing structures, properties, and functions. However, the current pharmaceutical market utilizes only THC containing medication, which cannot fully utilize the benefits of Marijuana. By showing the exact molecular mechanism by which cannabidiol interacts with glycine receptors, another means by which cannabis lead to analgesia has been established.

Foadi, N., et al. “Lack of Positive Allosteric Modulation of Mutated Alpha(1)S267I Glycine Receptors by Cannabinoids.” Naunyn-Schmiedeberg's Archives of Pharmacology. (2010): preprint.

March 2010: Cannabinoids have a role in reducing heart disease. (Shanghai Jiaotong University; Shanghai, China)

First some background: According to the World Health Organization (WHO), heart disease accounts for approximately 12 million deaths worldwide per year; and within the United States, about 2,600 people die per day from its complications. Although heart disease can manifest itself in several forms, the most common and most lethal is coronary artery disease, or atherosclerosis of the heart arteries. Atherosclerosis refers to the thickening of artery walls due to deposits of cholesterol shuttles such as LDL (low-density lipoprotein). Atherosclerosis develops when LDL molecules become oxidized by free oxygen radicals such as superoxide, a by-product of cellular reactions. Oxidized species such as the newly formed LDL cause damage upon contact with the endothelial cells lining arteries. When these cells are damaged, the body’s immune system tries to repair the damage and break down the oxidized LDL, but are unable to, and instead release more reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α). This starts a vicious cycle leading to greater and greater levels of inflammation, causing the artery to harden, narrow, and eventually be completely blocked. It is known that subtypes of immune system cells such as macrophages and T cells contain cannabinoid receptor 2 (CB2).

The new information: In this experiment, macrophages were isolated from model mice and rats and exposed to oxidized LDL in the presence and absence of a cannabinoid agonist. The levels of reactive oxygen species (ROS) and TNF-α as well as intracellular signaling molecules were then measured. It was found that in the absence of the cannabinoid, the oxidized LDL strongly induced the generation of ROS and TNF-α. However, in the presence of the cannabinoid, the levels of ROS and TNF-α were greatly reduced, which was shown to occur via a mechanism of inhibiting intracellular signaling pathways within the macrophage. When the macrophage was exposed to both cannabinoid and a cannabinoid receptor blocker, the oxidized LDL once again strongly induced the generation of ROS and TNF-α, suggesting that the reduction was a direct product of the cannabinoid.

What this means: By illustrating that cannabinoids effectively reduce the inflammatory response of macrophages to oxidized LDL, this study shows that cannabinoids may be used as a prophylactic measure in preventing coronary artery disease. Additionally, cannabinoids may have therapeutic benefits in the treatment of atherosclerosis, as it would greatly decrease further inflammation and the appearance of plaques. Therefore use of cannabis in patients with coronary artery disease may reduce their risk of heart attack.

Hao, M.X., et al. “The Cannabinoid WIN55, 212-2 Protects Against Oxidized LDL-induced Inflammatory Response in Murine Macrophages.” Journal of Lipid Research. (2010): preprint.

February 2010: Cannabinoids inhibit pain and bone loss induced by bone cancer (The University of Arizona; Tucson, Arizona)

First some background: Malignant bone cancer refers to a number of diverse tumor types, including osteosarcoma, chondrosarcoma, fibrosarcoma, cordoma, and Erwig’s sarcoma. Although the physiological mechanisms leading to tumor formation and malignancy may differ, the main symptoms of most forms of bone cancer are severe pain and bone loss. Thus, in standard treatment regiments for bone cancer, opiates are used in addition to chemotherapy and radiotherapy to abate the pain. However, use of opiates for analgesia has several downsides: physical addiction, high abuse potential, and rapid tolerance to name a few. Additionally, two side effects of chronic opiate use lead to an exacerbation of bone cancer symptoms. The first is pain hypersensitization. When the body is exposed to constant levels of any drug that acts as a receptor agonist, it induces a protective response to maintain its original state. Therefore when exposed to chronic opiate medications, the body reduces expression of opioid receptors, leading to decreased pain inhibition and thus increased sensitivity to pain. The second is hypogonadism. Opiates act on what is known as the hypothalamic-pituitary axis, causing decreased levels of hormone release. One of these hormones is GnRH (gonadotropin releasing hormone). GnRH causes release of two hormones from the anterior pituitary: LH (luteinizing hormone) and FSH (follicle stimulating hormone). These two hormones are responsible for regulating the amount of testosterone in both males and females. Although testosterone is widely known for being the main sex hormone in males, it is also present in lesser amounts in females with a common protective function of maintaining bone density. Thus chronic use of opiate medications will lead to an increased level of bone loss.

The new information: Cannabinoids have been shown to be a more valid alternative for treating bone cancer-mediated pain. The experiment was carried out by inducing bone cancer in mice and performing both behavioral and radiologic image interpretation of symptoms. After confirming the development of cancer, the mice were shown to have experienced both spontaneous and touch-evoked behavioral signs of pain. By administrating cannabinoids to the mice, both the spontaneous and stimulated pain was inhibited. Additionally, a sustained treatment regimen of cannabinoids led to significant reductions in bone loss, manifesting as a decreased likelihood of cancer-induced bone fractures.

What this means: By showing the benefits of utilizing cannabinoids as an alternative analgesic for bone cancer patients, cannabis may be a healthier alternative than opiates in treating pain associated with the cancer. Chronic use of opiates can cause more harm than good, as they often exacerbate the symptoms of bone cancer via patient hypersensitivity to pain and decreased bone mineral density. Cannabinoids on the other hand not only provide a non-physically addictive alternative, but also have been shown to attenuate the bone loss seen in cancer patients.

Lozano, A., et al. “A Cannabinoid 2 Receptor Agonist Attenuates Bone Cancer-induced Pain and Bone Loss.” Life Sciences. 2010: (preprint)

February 2010: Cannabinoids reduce the spread of damage following spinal cord injuries. (Hospital Nacional de Paraplejicos; Toledo, Spain)

First some background: The spinal cord is a bundle of nerve axons that descend from the brain down the back, to around the area of the waist. It is responsible for delivering and relaying messages traveling to and from the brain. The spinal cord is surrounded by bones known as vertebrae, which function to protect the spinal cord from damage or injury. However, it is still possible for damage to occur as a result of severe trauma, which tends to affect bodily functions below the area of injury. However, the initial trauma is not usually the major cause of cell death in the spinal cord. Necrosis occurs after a nerve cell axon is compressed, leading to swelling and eventually bursting. Additionally, a different process occurs known as apoptosis, or programmed cell death, in which neurons surrounding the initial area of damage receive a signal to essentially kill themselves. In spinal cord injuries this normally occurs in two waves: one wave eight hours after the initial injury that affects a specific cell type known as glial cells. The second wave occurs about seven days later in a different cell type known as oligodendrocytes, which can occur at areas distant from the epicenter of injury. This exacerbates initial damage and leads to increased loss of bodily functions.

The new information: It was found that by activating cannabinoid CB1 and CB2 receptors, neuronal axons were preserved at the immediate region of injury. Axons are long extensions of brain cells that form the actual spinal cord. These axons, also known as white matter, are coated with a fatty insulating material known as the myelin sheath, which is formed in the periphery by oligodendrocytes. It was shown that by activating these cannabinoid receptors, there was preservation of white matter and a decreased level of oligodendrocyte death at the epicenter. Additionally, the cannabinoid also inhibited myelin damage and oligodendrocyte loss at areas distant from the injury epicenter due to delayed apoptosis.

What this means: Currently, there are only two possible treatments for spinal cord injury that may help to halt the progression of neuronal damage: anti-inflammatory medication, and cold saline. Both of these work by decreasing the amount of signals that can be received by the cell processes in the spinal cord. However, anti-inflammatory medications may lead to an increased risk of infection, and administration of cold saline lacks empirical evidence to prove its effectiveness. This experiment showed that cannabis can possibly be used immediately following acute spinal cord injuries to decrease the amount of damage, and thus decrease the loss of function in patients.

Arevalo-Martin, A., et al. “The endocannabinoid 2-arachidonoylglycerol reduces lesion expansion and white matter damage after spinal cord injury.” Neurobiology of Disease. (2010): preprint.

January 2010: Cannabinoids inhibit a form of immunodeficiency due to HIV (Virginia Commonwealth University; Richmond, Virginia)

First some background: Immunodeficiency can be aptly described as the inability for the body's defense system to mount an effective response against invading pathogens, and is usually the result of a decreased number of white blood cells or a loss in ability to recognize the pathogen as foreign. HIV (Human Immunodeficiency Virus) leads to immunodeficiency via two main mechanisms: the direct killing of, or an increased rate of apoptosis (programmed cell death) in white blood cells. One of the cells that are targeted by HIV is the macrophage. Macrophages are involved in the initial response to an infection; foreign pathogens (i.e. bacteria) bind to surface receptors, causing the macrophage to envelop the bacterium and digest it. The macrophage then presents proteins of the digested pathogen to other cells, while also secreting chemical factors that attract other white blood cells. When macrophages are infected with HIV, they stop producing their own proteins and begin to produce and secrete viral toxic factors uncontrollably. One of these toxic factors is the protein Tat (transactivator), which serves as an attractant for monocytes, the precursor to macrophages. Once monocytes leave the blood stream and enter local tissues, they can develop into macrophages. By attracting other macrophages, HIV starts a vicious cycle leading to higher and higher levels of Tat in the human body. Additionally, Tat acts as a toxin by inducing apoptosis in T cells, one of the white blood cells responsible for mediating adaptive immunity. Adaptive immunity refers to the ability of the body to rapidly fight a pathogen upon re-infection. The death of the T cells leads to a loss in this adaptive immunity, which is a factor in the infection hypersensitization seen in HIV patients, especially those in which its progression has lead to the development of AIDS (Acquired Immune Deficiency Syndrome).

The new information: Administration of cannabinoids lead to an inhibition in the migration of monocytes due to Tat. By activating the CB2 cannabinoid receptor, it was shown that monocytes and macrophages did not respond to this attractive factor. The experiment proved this using three separate mechanisms. First, a cannabinoid receptor agonist was administered, which lead to the activation of the CB2 receptor on macrophages and inhibition of migration in response to Tat. Secondly, a cannabinoid receptor antagonist was administered, which blocks the CB2 receptor on macrophages and lead to migration. Lastly, the DNA of the macrophage was altered so that the CB2 receptor was not produced, and this lead to migration even in the presence of cannabinoid.

What this means: By halting one of the vicious cycles that lead to AIDS, cannabinoids can potentially stop the progression of HIV (AIDS is defined by a CD4+ (helper) T cell count below 200 cells per microliter). By decreasing the levels of HIV-induced release of Tat by macrophages, the level of T cell death due to Tat would decline. Thus, cannabis could potentially slow the progression of HIV and AIDS by disallowing widespread cellular infection. Currently, the standard treatment for HIV/AIDS is HAART (Highly Active Antiretroviral Therapy), which utilizes several of what are known as anti-retroviral drugs, which inhibit an enzyme responsible for converting the HIV genes into a format that can be read by human cells. While this form of treatment is effective in preventing cellular infection, it cannot target cells already infected with the virus. Therefore, macrophages already producing Tat will continue to produce it, attracting other macrophages for infection, and causing the continued death of white blood cells. By administering cannabis concurrently, it would add an additional level of protection by reducing the spread of HIV to attracted macrophages. Additionally, HAART is very expensive, with an approximate average cost of $1,500 per month. By utilizing cannabis in conjunction with more cost-effective anti-retroviral medications, the cost of treatment could be reduced to as little as $100 a month.

Raborn, E. and G. Cabral. “Cannabinoid Inhibition of Macrophage Migration to the Tat Protein of HIV-1 is Linked to the CB2 Cannabinoid Receptor.” The Journal of Pharmacology and Experimental Therapeutics. (2010): preprint.