Medicine Nobel For Studies On Inner Biological Clock

November 2017

Francisco J. Rojas, Ph.D.

The 2017 Nobel Prize in Medicine or Physiology was awarded to the scientists Jeffry Hall, Michael Rosbash and Michael Young for their discoveries of molecular mechanisms that control and drive circadian rhythms.

An essential feature of life on Earth is its capacity to adapt to profound changes in the environment. To adapt to daily changes in light and temperature, most organisms have evolved an internal biological clock that anticipates day/night cycles and helps them optimize their physiology and behavior. This internally generated cycle is known as circadian rhythms and exists in all forms of life, from unicellular bacteria to multicellular organisms, including plants, fungi, insects, rodents and humans.

That organisms adapt to the time of the day in a circadian fashion have been documented for a long time. But Hall, Rosbash and Young set out to determine just how our biological clocks function. They used as an experimental model the fruit fly (Drosophila melanogaster) to study the complicated process of circadian rhythms. This insect has a developmental process called eclosion, in which Drosophila emerges from its pupal case. Because pupae emerge only at a specific time of the day, the researchers can measure the timing between rounds of eclosion for different strains of flies and identify those that had a bad clock. By studying fly strains with timing problems they were able to zero in on the relevant gene that controlled this internal clock. The control gene, named Period was then isolated.

They found that Period gene encodes a protein called PER, whose oscillations in its levels inside the cells controls the organism’s biological clocks: the amount of PER protein accumulates in cells overnight before being broken down in the daytime. It means that levels of PER protein rose and fell over the 24-hour daily cycle.

One key discovery was that PER protein actually blocks the activity of the Period gene, creating a mechanism that allows PER to regulate its own levels throughout the day. This is called a negative feedback loop. As levels of PER protein build up over the course of the night, less and less PER protein is made; when dawn brakes, the protein levels eventually disappear and the process starts over again in a cycle manner. This series of steps repeats over and over each day with nearly exact timing. The discovery demonstrated that biological clocks use negative feedback loop from clock proteins like PER to turn themselves on and off again each 24 hours.

Later work by the researchers uncovered two other clock genes that are essential for the oscillation of the Period gene in the cycle. One is a gene that encodes a protein that allows PER protein to enter the cell nucleus to shut down the activity of the Period gene. The other is a gene that encodes a protein that degrades PER protein and thereby slows down its accumulation, helping synchronize the clock to the familiar 24-hour cycle.

How the cellular clockwork connects with the light-dark changes in the outside environment?  This is largely the job of the photoreceptor called cryptochrome protein which contributes to accurate timing by phase-shifting the clock in response to light. The capture of photon by cryptochrome (a blue light-absorbing substance) in the morning when the lights come on, leads to conformational change in cryptochrome. This conformational change leads to an interaction with the protein that degrades PER protein, which accelerates its decline, allowing cells set the time by the light every day.

The pioneered studies of this year’s Nobel laureates launched a subgenre of molecular biology that focuses on circadian rhythm. Though the genes differ from species to species, the key mechanistic principles for the biological clocks discovered by them, has been ultimately found in all organisms, from plants to Homo sapiens.

In humans, the clock regulates critical functions such as hormone levels, sleep patterns, blood pressure, heart rate, alertness, body temperature, metabolism, and behavior. So these discoveries have had important implications for health research and helped establish what is now called chronobiology, a growing field of science. As recognized by the Nobel committee, the work of Hall, Rosbash and Young is pivotal because the misalignment between a person’s lifestyle and the rhythm dictated by an inner timekeeper could affect well-being and over time could contribute to the risks for various diseases.


c&en, 98: 6, 2017




First Multi-Gene NGS Diagnostic Kit Approved

By: Francisco J. Rojas, Ph.D.

For the first time, the US Food and Drug Administration (FDA) has cleared a next generation sequencing (NGS)-based companion diagnostic that identifies multiple lung cancer mutations. The clearance marks the start of a new era in diagnostics, as the sequencing-based kit can be distributed to laboratories throughout the US, in contrast to ‘home brew’ tests, which are run only by the laboratories that developed them.


The new lung cancer diagnostic, named Oncomine Dx Target Test, was developed by Thermo Fisher Scientific (Waltham, Massachusetts), in collaboration with Novartis (Basel, Switzerland) and Pfizer (New York). Oncomine detects 369 variants in 23 genes in a single assay using one tumor specimen. Any of the variants on the panel can help an oncologist to make a treatment decision. In addition, the test acts as a companion diagnostic for some specific drugs including the combination of the drugs Tafinlar and Mekinist for the BRAF mutations, which the FDA approved on June to treat non-small-cell lung cancer patients.


The Oncomine platform is based on Thermo Fisher’s Ion ApliSeq technology, which requires 10 ng of nucleic acid to screen a tumor sample for multiple genetic markers. Although the technology is not as amenable for whole genome or whole exome sequencing, it’s very good at targeted sequencing from limited tumor specimens. Metastatic lung cancer biopsy samples are uniquely challenging because tumor biopsies often yield minute amounts. So the Oncomine’s minimal DNA/RNA requirement makes the panel testing for lung cancer feasible.


Researchers are particularly pleased that the kit was originally focused on in vitro diagnostic for lung cancer because this disease has many different molecular subtypes, which are targeted by a number of drugs or drugs in development. So the new test offers an analytically validated set of genes that allows understanding of the physiopathology of lung cancer and testing for the efficacy of new treatments and drugs.


We hope that Thermo Fisher will quickly expand the use of the new kit as a companion diagnostic tool for in vitro colon and other types of cancer covered by the genes on the panel.



Nature Biotechnology, 35: 699, 2017.

Nature Biotechnology, 34: 895, 2016

Reviewing Stories of Drug Use and Abuse So Far in 2017: ETG, NICOTINE, AND MORE

We have been following several important topics from both a scientific and societal angle throughout the year.  The previous series of posts highlighted the information and articles we found one category at a time.  This last entry is about a variety of subjects related to drug use and abuse. 


This article reports groundbreaking information about the cannabinoid receptor structure:


In February we posted two articles about the recent California legalization of marijuana.  The first revealed the political complications with California's marijuana legalization:

The second reviews the legal issues around marijuana legalization:


In March, Pyxis VP Dr. Francisco Rojas wrote a blog post about Kratom and its alkaloids.  We followed up the post with this article about the DEA ban on Kratom:


In April we highlighted this article about how EtG (a biomarker for alcohol metabolization) can detect alcohol usage in the urine:


Finally, in June we posted about the interesting ways that tests for substances like nicotine and cotinine are being applied:


Reviewing Stories of Drug Use and Abuse So Far in 2017: OPIOIDS

We have been following several important topics from both a scientific and societal angle throughout the year.  The next series of posts will highlight the information and articles we found one category at a time.  Next up is a collection of articles about opioids and the opioid epidemic.


Our first article on this subject posted in May after our VP Dr. Francisco Rojas wrote a blog entry on the relationship between pH and opioids:

May also brought this story about a novel way to use fentanyl tests for checking heroin:

In June we posted two articles.  The first is about an unexpected outcome of the opioid epidemic:

The second focuses on the complicated relationship between opiate addiction, treatment options and politics:


Two articles caught our attention last month.  The first is about gabapentin, a drug for nerve pain, that is quickly joining the ranks of abused painkillers.

The second is an article written for the American Association of Clinical Chemistry about the opioid epidemic: 


Reviewing Stories of Drug Use and Abuse So Far in 2017: SYNTHETIC CANNABINOIDS

We have been following several important topics from both a scientific and societal angle throughout the year.  The next series of posts will highlight the information and articles we found one category at a time.  We'll continue with a series of stories about synthetic cannabinoids.


In February, we posted this technical but interesting article about the chemistry behind UR-144:

In March we highlighted two articles.  The first is about DEA's attempt to classify synthetic cannabinoids as Schedule I:

The second focuses on risks of synthetic cannabinoids:

April brought an update about DEA's scheduling of synthetic cannabinoids:

In May, we focused on the biology of these substances.  This article explains the genetic factors and how the body processes synthetic cannabinoids:

Finally in June, we posted this fascinating article about the history of synthetic cannabinoids:


Reviewing Stories of Drug Use and Abuse So Far in 2017: DRUG AND ALCOHOL TESTING

We have been following several important topics from both a scientific and societal angle throughout the year.  The next series of posts will highlight the information and articles we found one category at a time.  We'll start with a fascinating collection of stories about drug and alcohol testing.


From January, an article about a Canadian roadside drug testing pilot program:

March brought us two articles.  The first is about the San Diego Police Department's roadside drug testing pilot:

The second is about the California legislature's attempt to set alcohol and drug cut-off levels:

In June we picked up a story about testing for marijuana intoxication in drivers in Sacramento:

Finally last month, we featured two articles about drug testing.  The first was a blog post from New Zealand about the varied role of drug testing:

The second is about drug testing in the Kentucky prison system:



The Rising Superbugs

By: Francisco J. Rojas, Ph.D.


A recent survey indicates that only half of Americans know that antibiotics kill bacteria but not viruses. The finding is in line with studies showing that one in four Americans visiting their health care providers complaining of a cold, expect their provider to prescribe them an antibiotic, falsely believing that the antibiotic will help them recover more quickly from the virus.

These false beliefs occur across countries and have contributed to a dangerous rise in antibiotic use. Worldwide sales of antibiotics by pharmacies and hospitals increased 36 percent between 2000 and 2010. But Americans are by far the highest per capita consumers. The Centers for Disease Control (CDC) estimates that 50 percent of all antibiotics prescribed in the United States are not warranted.

The overuse of antibiotics in medicine combined with the increasing use of antibiotics to grow livestock has led to the evolution of “superbugs”, lethal bacteria that are resistant to most antibiotics. This overuse most likely kills beneficial bacteria living in our guts and other parts of our bodies that protect us from infection. The drug-resistant bacteria then are more likely to take over and put us at high risk for resistant infections. These superbugs can spread to other people and in places such as the home, work or hospitals.

The loss of antibiotic effectiveness makes it more difficult to fight common infections, such as urinary tract infections and pneumonia. It also affects patients who often depend on antibiotics to recover from surgery, cancer therapy and other procedures. According to the CDC, each year at least 2 million Americans fight serious bacterial infections that are resistant to one or more antibiotics, and at least 23,000 die annually as a direct result of those infections.

How to combat the superbug threat? Changing incorrect public beliefs is essential. Many people still do not see antibiotic resistance as a personally relevant issue that presents risks to their health and the health of others. Health care providers are under huge pressure from patients to provide antibiotics for treatment of viral infections. In fact, research shows that a health care provider’s perceptions of patient expectations are a predictor of over-prescribing. The solution should be in advancing studies to better understand public behaviors and beliefs, and implementing public education campaigns that use effective communication and persuasion strategies.

But more than public education is needed. The widespread use of antibiotics in agriculture must be ended; clean water systems and sanitation must be built in poorer communities; scientific institutions and pharmaceutical companies must step up to develop new antibiotics; and importantly, health agencies need funding for detection and prevention of emerging superbugs.  Funding is also needed to change individual attitudes and health care practice or policy.

Hopefully we have learned some lessons from the topic of global warming. Government agencies were slow in recognizing the problem and educating the public,and are currently not supporting or underfunding initiatives aimed at reducing rising levels of greenhouse gas emissions. We cannot afford to delay investing in the efforts and specific actions needed to decrease the overuse of antibiotics and the spread of drug-resistant superbugs.



Hwang,TJ, et al, Lancet Infect Dis, 15: 1000, 2015

McCullough, AR, et al. J. Antimicrob. Chemother, 71: 27, 2016

Nisbet, M., SI, 41: 27, 2017

Watkins, LKF, et al. MMWR-Morbidity and Mortality Weekly Report, 64:767, 2015 

An Opioid Without Typical Side Effects

By: Dr. Francisco Rojas

Opioids are a class of strong analgesics widely prescribed to treat pain associated with tissue damage and inflammation, such as that caused by surgery, arthritis, nerve damage or cancer. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and is some cases, respiratory arrest. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and adequate pain management.

In a study published in Science this March, scientists from Charité-Universitätsmedizin Berlin and the Zuse Institute Berlin used innovative computational simulation to analyze interactions at opioid receptors -- the cell's docking sites for painkillers. They knew that when tissue is damaged and hurting, it becomes inflamed and more acidic. The pH drops from approximately 7.4, what is seen in normal, healthy tissue, to between 5 and 7. This means that there is an increase in the amount of protons floating around at the injury sites. So the researchers investigated what the extra protons may do to the binding behavior of opioids.

Through computer modeling the scientists found that the lower pH improved the binding of morphine-like molecules to their μ-opioid receptors. Based in this novel finding, they designed an opioid molecule that can be protonated to be active. The scientists ended up engineering a fluorinated version of the opioid fentanyl molecule, (±)-N-(3-fluoro-1-phenethylpiperidin-4-yl)-N-phenyl propionamide, or NFEPP for short.

Unlike the conventional opioid fentanyl, NFEPP showed pH-sensitive binding. The addition of the fluorine atom draws electron density from the fentanyl’s tertiary amine which results in a pKa of 6.8. Therefore NFEPP is protonated only in the acidic environment of peripheral injured or inflamed tissues. In the brain, however, where the pH is not low, NFEPP is not protonated and is consequently inactive. These observations indicate that the chemically modified fentanyl only activates opioid receptors on pain neurons at the site of the injury and not in the normal environment in the brain.

When used in a rat model, NFEPP demonstrated similar level of pain relief to fentanyl in different types of inflammatory pain but without exhibiting respiratory depression, sedation, constipation, or addiction potential. Healthy tissues remained unaffected, suggesting that the severe side effects associated with these types of painkillers might be avoided. Also, unlike fentanyl, high doses of NFEPP weren’t lethal to the rats.

The current discovery shows that designing drugs to activate under specific pathological conditions could be a new and valuable strategy for future drug development. We await further experimentation, testing and preclinical research. The data presented offers unprecedented hope of treating postsurgical and chronic inflammatory pain without causing side effects, which would considerably improve patient quality of life.


Science, 355:966, 2017

C&EN, 95:8, 2017

Kratom and its Alkaloids

March 2017

Francisco J. Rojas, Ph.D.

In August 2016, the US Drug Enforcement Administration (DEA) announced plans to designate mitragynine and 7-hydroxymitragynine, two alkaloid compounds that naturally occur in the leaves of kratom, as a schedule 1 substances. The classification was a de facto ban on kratom (Mitragyna speciosa), a plant indigenous to Southeast Asia.

Kratom leaves and the teas brewed from then are used by people across the globe to treat chronic pain, alcohol and opioid dependence, and anxiety. A review of websites and medical literature reveal that kratom have been increasingly used for the self-management of opioid withdrawal and pain in the United States. The DEA, however, considers the plant a danger to the public health. The agency has concerns that kratom produces adverse effects including narcotic effects and that its consumption can lead to addiction. By assigning kratom and its two alkaloids to the schedule 1 category, the DEA makes them illegal to manufacture, sell or possess with intent to sell.

The kratom community appealed to the DEA to delay their decision. People who take kratom say the herb helped them overcome addiction to opiates or alcohol and treat otherwise intractable pain. Others say kratom is not more dangerous than many other herbal supplements and much less harmful than prescription opioids. In addition, some researchers familiar with kratom say kratom's profile for both abuse potential and dependence liability is comparable to or lower than that of unscheduled substances such as caffeine, many antihistamines, antidepressants, and other substances sold directly to consumers. So people held rallies, started a “save kratom” online movement, and collected over 140,000 signatures. Citing the public outcry and a need to obtain more research, the DEA has since withdrawn its notice of intent and opened a public comment period. 

The DEA decision to withdraw the intent to ban kratom is a positive development. It comes just as there is a clear need for more science on the matter. Kratom contains chemical compounds, most notably mitragynine, 7-hydroxymitragynine, paynantheine, and speciogynine, along with more than 20 other substances. These compounds have complex and potentially useful pharmacologic activities and some of them produce effects similar to opiates when ingested.

Recent studies indicate that mitragynine and 7-hydroxymitragynine bind to and partially activate human µ-opioid receptors, the same receptors fully triggered by morphine. Also, it was reported that the compound mitragynine pseudoindoxyl, generated by fermenting mitragynine, is an even more potent activator of µ-opioid receptors than mitragynine and 7-hydroxymitragynine. Mice treated with a typical painkilling dose of mitragynine pseudoindoxyl experienced little respiratory depression, a common side effect of opioids such as morphine. These are early evidence of therapeutic potential for the plant compounds and their derivatives that can be produced semisynthetically.

Placing kratom in schedule 1 would complicate scientist’s ability to study the drug in the United States. Reversing the ban makes easy for investigators to obtain kratom and its constituent compounds for conducting research and the rigorous, controlled clinical trials that are needed to assess their safety and efficacy. The work with kratom is promising; it may have beneficial effects particularly in the management of both opioid withdrawal and pain. The few available scientific data also suggests that kratom its compounds and derivatives could eventually lead to the development of non-addictive medications to powerful opiate painkillers.



J Am Chem Soc, DIO:10.1021/jacs,6b00360

JMed Chem 2016, DIO: 10.1021/jmedchem.6b00748

c&en, 94 (36), p5, 2016


Cannabinoid receptor structure revealed

By: Francisco J. Rojas, Ph.D.

 Marijuana, the cannabis plant, is a psychoactive (mind-altering) drug that contains compounds called cannabinoids. The plant’s primary drug effects come from the chemical delta-9-tetrahydrocannabinol, or THC. Individual cannabinoid chemicals may be isolated and purified from the marijuana plant or synthesized in the laboratory, or they may be naturally occurring (endogenous) cannabinoids found in the body.

There is a growing body of research suggesting the potential therapeutic value of cannabinoids in numerous health conditions including pain, nausea, epilepsy, obesity, wasting disease, addiction, autoimmune disorders, and other conditions. However, some cannabinoids can cause side effects, such as dizziness, hallucinations, and paranoia. Some synthetic cannabinoids, such as K2 or Spice, can produce severe and even deadly reactions.

Cannabinoids exert their primary effects in the brain by binding the human cannabinoid CB1 receptor. Determining the detailed 3-D structure of this receptor is important for potential drug development, as it provides key details about how the receptor and drugs might interact. Last October an international group of scientists published an article in the journal Cell reporting the structure of the CB1 receptor. Their work was funded in part by NIH’s National Institute on Drug Abuse (NIDA).

The scientists synthesized AM6538, a THC-related chemical they designed to help crystallize the CB1 receptor. AM6538 inactivated and slightly modified the CB1 receptor to optimize it for crystallization. They then computed the 3-D structure of the CB1 receptor-AM6538 complex using X-ray crystallography, in which the angles and intensities of X-rays that bounce off a crystal structure are used to determine molecular shape.

The crystal structure revealed that the CB1 receptor has a complex binding pocket with multiple subpockets. Based on prior observations, the scientists were able to predict how other cannabinoids, including THC, would fit into the receptor and how different cannabinoids may interact with the receptor. The findings provide a model to investigate how long each cannabinoids might bind to the CB1 receptor and how each cannabinoid would exert different structural modifications to the receptor.

The interest in the possible therapeutic uses of marijuana is considerable. With Americans across the country consuming marijuana and its constituent compounds for health related conditions, there is a pressing need for well-controlled studies related to their health effects and potential risks, and for more basic research on the biochemical properties of cannabinoids and the physiological systems they affect. The present study on the structure of the CB1 receptor and mechanisms by which different cannabinoids can cause somewhat different effects, will surely help the progress of therapeutic development and clinical trials.



Following Stories of Drug Use and Abuse in the News

The spike in drug abuse, especially in the United States and Canada, has been receiving a lot of media attention and for good reason.

This NPR story from September 12, 2016 about use in the U.S. states:

A report set to be released Tuesday shows a more than thirteenfold increase in spending by health insurers in a four-year period on patients with a diagnosis of opioid dependence or abuse.

Read the rest of this story here:

The local Vancouver radio station CKNW filed the following story on September 21, 2016:

488 people have died in BC as of the end of August as a result of illicit drug use.  That’s a 62 per cent spike over the same time last year.

Check out the entire report here:

Overall drug positivity has increased for the 5th year in a row with the highest drug use being amphetamines, heroin, and marijuana according to this Quest Diagnostics Analysis:

John Oliver used his HBO show Last Week Tonight to take a look at how opioid use and abuse affects everyday Americans:

There is little doubt that abuse and subsequent deaths are rising worldwide.  Perhaps media attention will lead to action in the form of policy changes and honest examination of how these drugs are prescribed and managed.




Naloxone and the Opioid Epidemic

By: Dr. Francisco Rojas

Naloxone is an antagonist that competes for the same receptors as opioid agonists such as heroin and fentanyl. Naloxone pushes those drugs out and takes their place, but it doesn’t turn on the opioid receptors when it binds to them, so it produces no opioid high. Because naloxone prevents those other opioids from acting, it is used in opioid overdoses to counteract life-threatening depression of the central nervous system and respiratory system, allowing an overdose victim to breathe normally. Although naloxone is a prescription drug, it is not a controlled substance and has no abuse potential.

In the past 15 years, the death rate from prescription opioid-associated overdose nearly quadrupled from 1999 to 2013, while deaths from heroin alone more than tripled from 2010 to 2014.Together, heroin and prescription pain medications take the lives of more than 28,000 Americans per year —over 75 people per day. They also cause hundreds of thousands of non-fatal overdoses and an incalculable amount of emotional suffering and preventable health care expenses.

The synthesis of naloxone was the result of chemical modifications of other opioids. Chemists knew that adding a hydroxyl group to the carbon next to an opioid’s amine would increase the drug’s potency. This is the case for oxymorphone, which has this alcohol group and is 10 times more potent as a painkiller than morphine. However, replacing the methylamine group of oxymorphone with an allylamine, the result is the antagonist naloxone. The new compound was found to reverse the effects of every opioid they tested it against. Jack Fishman and Mozes Lewenstein filed for the U.S. patent on naloxone in 1961.

FDA approved naloxone for treating opioid overdoses in 1971. Before 2014, the only approved way of delivering naloxone was via injection, either into a vein or a muscle. But giving an injection can be difficult for someone without medical training. Fortunately, two new products have recently been approved by the FDA: An autoinjector called Evzio in 2014, and last November a nasal spray under the name of Narcan.  They are easy to use and effective at reversing overdoses. In a human use trial that was required for approval, 90% of first-time users were able to use the spray correctly. This data will encourage more widespread naloxone use in the U.S., and hopefully, help keep prices for the devices down. The ability to reverse an opioid overdose is highly dependent on time elapsed since ingestion. So it‘s expected that expanding access to these devices to people who might be present during an overdose, will extend the small time window in which an overdose can be reversed before brain damage or death occurs.

Access to naloxone has historically been limited by laws and regulations that pre-date the overdose epidemic. In an attempt to reverse the unprecedented increase in preventable overdose deaths, the majority of states have recently amended those laws to increase access to emergency care and treatment for opiate overdose. These changes come in two general views. The first encourages the wider prescription and use of naloxone by clarifying that prescribers acting in good faith may prescribe the drug to persons who may be able to use it to reverse overdose and by removing the possibility of negative legal action against prescribers and lay administrators. The second encourages bystanders to become “Good Samaritans” by summoning emergency responders without fear of arrest or other negative legal consequences. The effort is to get naloxone into the hands of friends, family members, and other bystanders.

Not everyone agrees naloxone is beneficial. Critics say that naloxone does not truly save lives; it merely extends them until the next overdose. They imply that naloxone will only foster addiction and that it gives drug users a safety net, allowing some to overdose numerous times in safety. Interestingly, similar criticisms were argued about needle exchange programs to fight HIV. Critics delayed the implementation of the program because it was encouraging more risk taking. But when New York state expanded access to clean needles, HIV infection rates in drug users fell from 54% in 1990 to only 3% by 2012.

So let’s not make the same mistake with the opioid epidemic by promoting baseless and ill informed fears about naloxone. We need to push for making the drug available to anyone who might witness an overdose and can respond more quickly than paramedics. Policy decisions on the opioid crisis must be made based on science, not stigma. Addiction is a disease. We must treat it with the same urgency, humanity and compassion as we treat all diseases.


Rudd, R.A., Aleshire, N., Zibbell, J.E., Gladden, M., 2015. Increases in Drug and Opioid Overdose Deaths —United States, 2000–2014. Morbidity and Mortality Weekly Report (MMWR) 64, 1-5

Chemical & Engineering News, May 16, 2016, p34.


Proposition 64

Being a California-based company, Pyxis is continuing to focus this month on the legal status of marijuana.  On November 8, California voters will be asked to consider Prop 64, which effectually legalizes the use of marijuana for adults:,_Marijuana_Legalization_(2016)

As of this August 19 Los Angeles Times article, the initiative is set to pass:

The implications, of course, are huge and multi-faceted.  California is an economic behemoth with industries ranging from agriculture to entertainment to tech and biotech.  As this CNBC story illustrates, the economic boom could be viewed as another Gold Rush:

California would join Colorado, Washington, Alaska, and Oregon in legalization of recreational THC use.  This article we posted in July from the Boston Globe does an excellent job at highlighting both the benefits and the challenges that Colorado has faced since legalization:

But California is unlike any of the previous states that have legalized marijuana, and if Prop 64 passes (as it looks set to do) the effects, both economical and social, will be as unique as our state.

Marijuana Legalization

We have been carefully watching the cultural and political implications of the increasing legalization of marijuana.  Like anything else, it seems to be a matter of striking a comfortable balance between the needs of everyday citizens, police, and the medical community to name only a few of the interested parties.  Here are some interesting articles we've shared this past month:

Positive correlations between medical marijuana and lowered opiate use: #opiateAbuse

Great Boston Globe article about how legalization of marijuana has affected Colorado: