TIME Addiction

Viewpoint: FDA Approval of Overdose Antidote Leaves Lives on the Table

Making the epi-pen available by prescription is just the first step. It also needs to be available over the counter.

The FDA approved on Thursday the equivalent of an “epi-pen” for overdose prevention, an antidote auto-injector that even untrained people can use to save the lives of those who have overdosed on drugs like Vicodin or heroin. Such opioid overdoses kill around 17,000 Americans each year.

While this first step is welcome, the antidote remains prescription only. But to save the most lives, it needs to be made available over-the-counter and be affordable enough to be included in every first aid kit in the country.

While it’s commonly thought that the only people who die of overdose are people with addiction, in fact, OD kills in many different scenarios. Grandma might mix up her meds and take them twice or even three times. Uncle Bob might forget that pain medication and alcohol shouldn’t mix. A toddler or a curious teenager might get into the medicine cabinet. And someone who struggled with addiction in the past might relapse: the highest risk times for overdose in addiction are initial use and then middle age, with peaks that also occur after periods of abstinence or incarceration. In many of these situations, relatives don’t realize that their loved one is at risk.

Another myth about overdose is that it typically occurs when people are alone. Research suggests that at least half of all overdoses are witnessed, but oftentimes the witnesses don’t know what they are seeing and “let them sleep it off,” which is basically the worst thing to do. Instead, if someone’s breathing is slowed or stopped, their skin is bluish, you cannot arouse them, and there’s any chance that overdose is the cause, calling 911, using naloxone, and performing rescue breathing is best.

Combined with greater awareness of these OD symptoms, the new drug delivery system could make a real difference. Called Evzio, it’s basically a sophisticated epi-pen. But instead of containing adrenaline to prevent potentially fatal allergic responses, it contains naloxone, a nontoxic FDA-approved drug that can instantly reverse potentially fatal overdoses that include opioids. (At least 2/3 of overdoses involve drug mixtures, but if one of the drugs is an opioid, Evzio will still work).

Evzio also has safety features that prevent the needle from being re-used, and recorded audio instructions that can guide people without prior training in how to save a life. There’s virtually no way to misuse it. Essentially, naloxone causes the opposite of a high and can induce distressing withdrawal symptoms in people who are addicted. Since the experience of being revived with it is unpleasant, using Evzio as “insurance” for excess that wouldn’t otherwise occur is unlikely to be a major issue. And it won’t harm even if given in error; since the only thing it does is block opioids, it doesn’t hurt in other types of OD or in other situations that cause people to lose consciousness.

Research already shows that making naloxone available to lay people in other forms is effective. A study of Massachusetts’ program published in BMJ found that not only did an intranasal version of drug revive 98% of victims to whom it was administered, it also cut the OD death rate in regions with high levels of availability by nearly 50%, compared to areas where it was less accessible.

MORE: Wider Distribution of Overdose Antidote Could Cut Death Rates By Nearly Half: Study

Since 1996, when activist Dan Bigg started the first naloxone distribution program in Chicago, around 200 such programs have sprung up in the U.S. Collectively, they’ve distributed more than 50,000 doses with at least 10,000 reported revivals. No serious side effects have come to light. The drug has been used safely in hospitals since the 1960s, and was approved for such use by the FDA way back in 1971. Last month, attorney general Eric Holder even urged that states make it available to all first responders. New York state announced Thursday a $5 million program to distribute it to police officers.

Experts agree that in an overdose situation, “time is brain.” The longer someone goes without oxygen, the worse the consequences and the more likely the overdose will be fatal. No parent I’ve spoken with has ever said that they would prefer not to have such a drug on hand if they ever came upon a blue and unconscious child.

Given this, and naloxone’s spotless safety record, there’s no reason to require prescriptions for it. And since no one can truly predict where and when an OD might occur, it should always be nearby if possible; hence first aid kits are the natural place for it. If everyone has it, no one has to feel singled out as potentially having an addicted person in the family; it’s just there for emergencies that could actually affect anyone.

Dr. Eric Edwards, the chief medical officer of Kaleo Inc., which makes Evzio, says that given naloxone’s safety profile, it’s possible that it may be made available over the counter in the future. “We think this is the first step to building the safety data needed to show that it can be used appropriately,” he says.

But people are dying every day, right now. It has taken at least 18 years from the time Bigg first distributed naloxone to get to this place, and more than four decades since the FDA originally approved naloxone for hospital use. Even the director of the National Institute on Drug Abuse, the agency charged with addiction research in the U.S., says it should be over-the-counter.

Says Bigg, “It sounds like [Evzio] is a big step forward, if it is affordable.” The price has not yet been made public.

And regardless of the price issue, is there really any reason to wait any longer to allow all types of naloxone to be sold over the counter? The FDA can choose to act on an emergency basis in terms of drug approvals if it so desires. With the availability of Evzio, there’s no justification for not doing so, other than the ongoing stigma of addiction.

MORE: Overdose Antidote Is Cost Effective at Saving Lives

TIME

Suicidal Impulses Don’t Have to Be Deadly

Suicide Barrier Could Be Installed On Golden Gate Bridge
A sign alerting people to use an emergency crisis counseling phone if in distress. Justin Sullivan—Getty Images

Safety nets, which will go up around San Francisco's Golden Gate Bridge, are a proven lifesaver

For more than six decades, Californians have resisted the idea of adding barriers to the iconic Golden Gate Bridge to prevent suicide. Now, after a record 46 deaths in 2013, the authority that oversees the bridge are expected to reverse course. But will this simply divert those drawn to the most popular suicide spot in the U.S. to other bridges or methods?

The research in the area is surprisingly clear, at least on this count. Although nearly 40,000 Americans die from suicide every year—a death toll similar to that from unintentional overdose and car accidents—most suicide attempts that are foiled are not repeated. The majority of suicides are committed on impulse.

Kevin Hines, who survived an attempt 13 years ago, immediately regretted hurdling himself over a railing of the Golden Gate Bridge. In the short amount of time it took him to hit the water, Hines had already changed his mind and positioned himself to try and survive the fall. He shattered two of his lower vertebrae, but lived to tell about it.

A 1977 study [PDF] found that 94% of the 515 people who were stopped from leaping from the Golden Gate between 1937 and 1971 were still alive, an average of 26 years later.

And that isn’t the only data suggesting that deterring suicide by one means doesn’t merely shift people to another. Studies [PDF] of bridge barriers from Maine to New Zealand find that installing them is linked with a reduction in deaths, while removing them increases mortality.

Moreover, the same holds true for other methods. Research from Sri Lanka, where a common means of committing suicide is ingesting pesticides, found that after the most toxic pesticides were restricted in the mid ‘90s, the suicide rate was cut in half within 10 years. A similar drop in suicide was seen in Great Britain when carbon monoxide was removed from the gas used in cooking, preventing people from taking their lives the way poet Sylvia Plath infamously did, by sticking her head in the oven.

Although it’s commonly believed that rumination and suicidal thinking occur long before people actually try it, a study of people who made nearly fatal attempts found that a quarter had only thought about suicide for five minutes before trying it, and nearly 90% had deliberated for just eight hours or less.

This is why guns are strongly linked to suicide: they make the odds that a passing impulse will be deadly much higher, and account for nearly half of all suicide deaths. Unlike deliberate overdose attempts, which are fatal only around 3% of the time, guns kill 85% of those who use them to attempt suicide.

As a result, states with higher rates of gun ownership have gun-associated suicide rates that are four times higher in men and eight times higher in women, while rates of suicides by other means are no different, according to a 2007 study.

The link to impulsivity may be one reason that suicidal thinking is relatively common but suicide itself is far more rare, and predicting who is at highest risk is difficult. Nearly 4% of those over age 18 reported thoughts of suicide in the past year, according to the CDC, and 10-20% of teens say they have considered suicide over the course of their lifetimes. But only around half a percent of adults and 2% of youth annually report actually having made an attempt. Obviously, those who are there to report having made an attempt did not succeed.

Tad Friend, writing in The New Yorker in 2003, when California was resisting adding a barrier to the Golden Gate, put it this way:

[T]o build one would be to acknowledge that we do not understand each other; to acknowledge that much of life is lived on the chord, on the far side of the railing. Joseph Strauss [the chief engineer who designed the bridge] believed that the Golden Gate would demonstrate man’s control over nature, and so it did. No engineer, however, has discovered a way to control the wildness within.

Now, however, at least a few more souls will be saved from desperate impulses—and a few more families spared the incomparable heartache and loss that death by suicide brings to loved ones.

TIME

A Medication to Treat Anorexia?

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Getty Images

Evidence that a brain chemical called oxytocin can help autistic people pay more attention to social cues is prompting some researchers to examine whether the drug could have any impact on those battling with anorexia, which lacks a pharmacological medication

Autism and anorexia have wildly different public faces. The stereotype of an autistic person is a little boy obsessed with trains or a brilliant coder with no social life, while the eating disorder victim is typically pictured as a driven young woman or girl, whose whole world revolves around presenting a carefully drawn picture of thinness and social perfection.

While stereotypes never capture the whole story, underlying both conditions is a rigid obsessiveness that appears within the first few years of life, as well as difficulties reading and responding appropriately to social signals. Not to mention, two of the major triggers for anorexia are a profound sense of alienation and sensitivity to social ranking, according to Dr. Janet Treasure, professor of psychiatry and director of the eating disorders unit at King’s College in London.

Evidence that oxytocin, a brain chemical also known as the “love hormone,” can help autistic people pay more attention to social cues and make socializing less stressful prompted Treasure to explore what effect it would have on anorexia. Now, three new studies of the hormone—best known for its role in bonding lovers to each other and parents to their children—suggest that it may indeed be a viable treatment for anorexia, which currently has no effective pharmacological medication and relies for the most part on therapy.

In the first study, published in Psychoneuroendocrinology, when anorexic women were given placebo and asked to look at images of food or pictures of various body parts or shapes that were either thin, fat, or not associated with weight (like eyes), they paid much closer attention to food pictures and to the fatter body shape images than the healthy control group. But when they were given intranasal oxytocin, they showed less interest in the food and shape-related pictures, making their reactions more like those of the healthy women. Moreover, the more autistic traits the women with anorexia had—for instance, a preference for repetition and sameness, strong interests, and difficulty reading people—the more effective oxytocin was at normalizing their responses.

In a second study, published in PLOS ONE, oxytocin was found to decrease the attention anorexic women paid to disgusted faces, while increasing vigilance to angry ones. “Disgust is very much a signal of not being ‘in with the in crowd,’” says Treasure. “I think people with anorexia do feel those putdowns and social ranking [very intensely].” And when it comes to rage, “anorexic patients suppress anger a lot,” says Treasure, “and yet, inside, they have a lot of anger and frustration.”

Dr. Eric Hollander, Director of the Autism and Obsessive Compulsive Spectrum Program at Albert Einstein College of Medicine and Montefiore Medical Center, who was not associated with the study, agrees that people with anorexia often find anger unacceptable or even toxic in themselves and others. Consequently, he says, “they develop these habits where they [react to] those emotions both through restriction of food and feelings of low self worth.”

Environmental exposures and experiences can affect which genes for oxytocin receptors are expressed and therefore, influence behavior. So in a third study Treasure and her colleagues looked at how anorexia affects the expression of these genes. What they discovered was that women with anorexia did have some specific variations in the expression of oxytocin receptor genes, which might reduce levels of the hormone and cause a deficiency. These changes were linked with the severity of their disorder. It’s unclear, however, whether these alterations predispose women to anorexia or whether they are caused by starvation, which is known to affect gene expression.

The new studies “suggest that within anorexia, there’s a dimension related to autistic-like behavior,” says Dr. Hollander. Researchers like Treasure have previously suggested that anorexia might, at least in some cases, be a form of autism seen more commonly in girls. A girl with a rigid desire for sameness and an obsessive bent might be more likely to focus her interest on food restriction in a culture that prizes thinness in girls, while a boy with those same tendencies might develop more typically autistic obsessions. And some research has found that the same genes can influence risk for both conditions.

MORE: A Genetic Link Between Anorexia and Autism?

Aside from the intriguing link between autism and anorexia, all three studies point to a new direction for anorexia research that focuses on treating its underlying biology, rather than changing psychological factors. “It needs to be much more brain directed,” says Treasure. “Talk therapy can only do so much.”

TIME Overdose

What Philip Seymour Hoffman’s Sponsor Could Have Done for Him

"A Most Wanted Man" Portraits - 2014 Sundance Film Festival
Hoffman at the 2014 Sundance Film Festival in Park City, Utah. Larry Busacca—Getty Images

As part of Twelve-Step programs, they act as support, friend, mentor, and advisor—but they're also former addicts and shouldn't be treated as experts

A haunting writeup in The New York Times Thursday detailed how actor Philip Seymour Hoffman spent his last days after relapsing back into heroin addiction and leaving the home he shared with his partner, Mimi O’Donnell, and their three children.

Though he was surrounded by people as the end drew near, the Times piece describes how Hoffman was ultimately “a man who died alone”—which is sadly not uncommon for addicted people. Notably included was a quote from a member of the Twelve-Step program Narcotics Anonymous (NA) regarding what the actor said at a December meeting. Though speaking about what was said by a specific person meeting is an unusual breach of protocol, the incident has got people thinking about what goes on in NA meetings and the idea of members “sponsoring” each other to support recovery.

As a former heroin and cocaine addict who has covered addiction and recovery for over a quarter century, I’d like to stress that I am writing here as someone with knowledge of the field and not as a member of any program. There are many routes to recovery and Twelve-Step programs are just one.

MORE: Philip Seymour Hoffman Didn’t Have to Die

Although touted as an essential element of Twelve-Step recovery, the guidance given to sponsors is extremely vague. There is no requirement for having a certain amount of time drug-free, although at least 90 days is typically required and, most commonly, at least one year. Moreover, there are no specific guidelines related to the amount of contact people should have with their sponsors and the type of advice that should be given at any particular time. An NA pamphlet puts it this way:

Sponsors share their experience, strength, and hope with their sponsees. Some describe their sponsor as loving and compassionate, someone they can count on to listen and support them no matter what. Others value the objectivity and detachment a sponsor can offer, relying on their direct and honest input even when it may be difficult to accept. Still others turn to a sponsor mainly for guidance through the Twelve Steps.

From the outside, the idea that a more experienced member should sponsor someone who is new or has recently relapsed looks like a way to help the newcomer. But, in fact, Twelve-Step literature explicitly says that this is not the purpose, although it is obviously a welcome result. The sponsor-sponsee relationship is predicated on the assumption that “‘the heart of NA beats when two addicts share their recovery,’” and “sponsorship is simply one addict helping another. The two-way street of sponsorship is a loving, spiritual, and compassionate relationship that helps both the sponsor and sponsee.”

In practice, of course, this means that sponsors do give advice and support to newcomers—and anyone who has spent time around people in recovery knows that they will often go to enormous lengths and spend much of their time to try to help.

But the pamphlet also notes that a sponsor is not “a legal advisor, a banker, a parent, a marriage counselor, or a social worker. Nor is a sponsor a therapist offering some sort of professional advice.”

Unfortunately, many sponsors do provide medical advice, which can pose a problem for people whose issues are complex and who require psychiatric care, not just group support, which is at least half of all people with addictions. Both NA and Alcoholics Anonymous have had to warn [PDF] members not to “play doctor” in this way since suicides have occurred when people stopped taking needed medication. While recent years have brought greater acceptance of medication use, the issue of clashing advice from sponsors and professionals remains.

This issue is most acute when it comes to the long-term use of medications like methadone or Suboxone to treat heroin and other opioid addictions, NA sponsors have traditionally viewed this practice as “not recovery” and as violating the program’s basis in complete abstinence because these medications are themselves opioids. But research shows that these medications can cut death risk for people with heroin addiction by around 70% [PDF]—and some have argued that the stigma against maintenance is part of what killed Hoffman.

NA has struggled for years to address the controversy, traditionally not permitting those still on medication to share in meetings, be sponsors, or hold leadership positions. In many NA groups, such people are seen as having no days in recovery until they stop maintenance. As of 2007, however, the organization has taken the position [PDF] that it is up to individual groups to determine whether people on maintenance have equal status.

As all of this illustrates, addiction and recovery are complicated. There simply is no one true way to get better. Consequently, the humble stance advocated in the Twelve Steps (and perhaps practiced more in the breach than in the appropriate spirit) is a good recommendation both for those who act as sponsors and for anyone else trying to cope with addiction.

MORE: Amy Winehouse and the Pain of Addiction

TIME Child abuse

Dylan Farrow’s Child Abuse Accusations: What We’ve Learned About When, and How Children Should Confront Abuse

Experts still don't have all the answers, but have a better appreciation for how to help young victims confront their abuse experience

Dylan Farrow’s open letter responding to her adoptive father Woody Allen’s lifetime achievement Golden Globe reignited the child abuse questions that captivated the media in 1993, when Farrow’s mother, Mia, then Allen’s girlfriend, split from the director. Then seven-year old Farrow’s claims that Allen had raped her became the lynchpin of a bitter custody battle; Allen continues to deny the claims, and was never prosecuted.

Farrow’s letter provides an opportunity to understand what psychologists have learned about when it’s too early to address child abuse with victims (making it too traumatizing) and when it can do harm (if children are forced to relive the experience without proper support). In the years since, some experts say, they have come to a slightly better, although still emerging sense of how reliable childhood memories and recollections are, and the lasting impact of abuse on survivors.

MORE: Woody Allen Lawyer Says Dylan Farrow Is Mia’s ‘Pawn’

While cases of sexual abuse involving children have declined since Allen was first accused— between 1992 and 2010, the number of substantiated abuse cases fell by 62%, according to the National Child and Abuse Neglect Data System and other databases— around one in five girls in the U.S. still suffers at least some form of sexual molestation during childhood.

In about a third of those cases, affecting 6% to 7% of girls overall— the perpetrator is a family member, according to David Finkelhor, the director of the Crimes Against Children Research Center at the University of New Hampshire. But the most common perpetrator is a non-family acquaintance, such as a neighbor, the older sibling of a friend or a coach or teacher, he says. Abuse by strangers — the stereotypical accoster in the park or kidnapper in an unmarked van— only occurs in about 3-4% of cases.

In the 1980s and 1990s, the prevailing principle guiding sexual abuse cases was “believe the children,” which experts hoped would give young victims the benefit of the doubt when confronting potential adult abusers. But that led to dozens of wrongful convictions, particularly of daycare personnel and in cases with little or no physical evidence . Now, says Finkelhor, “The field is much more cautious about child testimony.”

That’s because psychologists are learning more about how repeated interrogation and the experience of testifying affects memory and recollections, particularly among young children. Studies showed, for example, that false convictions tended to result when children were constantly interrogated with leading questions or pressured to “tell the truth” that the interrogator wanted to hear. “There have been all kinds of protections developed in the last 20 years about how to talk to children in the course of investigations so as not to create confabulation or not to impair the testimony so it could be impeached in court,” says Finkelhor. For example, using anatomically correct dolls has been shown to produce false testimony, so investigators no longer use them.

Still, the truth is especially difficult to discern during custody cases. “The [studies] show that in some cases these are true allegations that emerge because the family is no longer trying to keep [itself] together and hide this particular secret, but that in some situations it seems to be an allegation that doesn’t have support and is probably not true,” Finkelhor says. No one really knows how common false allegations are in custody trials— but clearly neither the extreme view that they never happen or that all reports are true is correct.

And since the end of the 20th century, dozens of studies have shown how fragile and unreliable memory can be. More work even shows that it is possible to implant false memories in both adults and children using very simple prompts and suggestions. In an interview with TIME last year, Elizabeth Loftus, professor of psychology at the University of California in Irvine, noted that in her research, she was able to implant a false memory of witnessing Satanic possession, albeit in only a minority of participants. “I’ve been planting bits of false memory in my experimental work for decades,” she said. In response to Farrow’s letter, one of Allen’s attorneys says Farrow’s recollection of the abuse that occurred 20 years ago was planted by her mother.

MORE: Fighting Excess Drinking with False Memories

But that doesn’t mean that children — or adults for that matter — cannot ever testify accurately. The age of the child, his or her own level of maturity and the circumstances of the abuse all play a role in credibility. The older the child, the more reliable their memory can be, but unfortunately, child predators tend to prey on the youngest and most vulnerable who are least likely to be believed.

And that means that when a young child is victimized, it’s difficult to determine whether subjecting him to a court experience, and forcing him to testify, will be helpful or harmful to their recovery. “These cases are very hard on children, whether they testify or not,” Finkelhor says. Research shows that testifying itself doesn’t necessarily increase or decrease the child’s trauma— but what does matter is how long the proceedings drag on and how the parents respond to the child. The longer the case takes, the worse the outcome— for instance, children can develop post-traumatic stress disorder, depression, suicidal thoughts or addictions. Also important is how willing the child is to testify and what fears he or she has in connection with doing so. “Having support from their primary caregivers is crucial,” says Finkelhor.

MORE: When Seeing the World As Good Can Hurt Sex Abuse Survivors

Farrow wrote: “That [Allen] got away with what he did to me haunted me as I grew up. I was stricken with guilt that I had allowed him to be near other little girls. I was terrified of being touched by men. I developed an eating disorder. I began cutting myself.” Would she have felt the same way if she had testified at age seven? That’s an open question that experts are still trying to answer. Farrow, now happily married, credits the support of family and friends for helping her to confront those emotions— as well as the survivors of sexual abuse who, she wrote, “have given me a reason not to be silent, if only so others know that they don’t have to be silent either.”

TIME Drugs

Philip Seymour Hoffman Didn’t Have to Die

Philip Seymour Hoffman in Los Angeles, Nov. 18, 2013.
Philip Seymour Hoffman in Los Angeles, Nov. 18, 2013. Robyn Beck / AFP / Getty Images

There are ways to prevent loved ones from becoming victims of an overdose. Here are three.

Philip Seymour Hoffman has joined Heath Ledger and Cory Monteith in the tragic ranks of talented actors killed by opioids, the class of drugs that includes heroin and prescription pain relievers like Vicodin. The Oscar-winning star of Capote and The Hunger Games was found on the bathroom floor of his New York apartment yesterday, with a needle still in his arm and eight empty envelopes of the type that usually contain heroin nearby. He was just 46.

Opioid drugs aren’t only killing celebrities— poisoning deaths, most of which are due to drugs, have actually overtaken car accidents as the leading cause of accidental death in the U.S., responsible for nearly 40,000 fatalities annually. But those numbers don’t need to be so high. Although preventing opioid addiction is difficult, preventing deaths from it is far simpler. The majority can be avoided with simple measures — such as knowing the signs of overdose and keeping a nontoxic antidote available in first aid kits— that the U.S. has been slow to adopt. The stigma of addiction and the lack of organized advocacy for affected people have been the biggest barriers to change.

Whether it’s a heroin addict who has relapsed, a toddler who gets into grandma’s oxycontin, a granddad who drinks and takes the wrong pills or a teenager who tries these drugs in a dangerously high dose, there are ways to prevent these individuals from becoming victims of an overdose.

1) Be an active witness.

While people tend to imagine that overdoses primarily occur when drug users are alone, in fact, at least half of them happen in the presence of others. In England, for example, 80% of users who overdosed did so while with others and 54% had also witnessed others who had OD’d. A study in New York similarly found that 57% of over 1,000 crack and heroin users had personally witnessed at least one overdose. A Rhode Island study revealed that 35% of opioid users had overdosed at least once themselves and two-thirds had seen someone else do so.

While we don’t know whether anyone was with Hoffman when he injected the drugs that likely killed him, if he was not intentionally seeking suicide, it’s possible that someone might have been with him at some point during the one to three hours it typically takes for opioids to kill. And if his injection was witnessed and that person had known the signs of overdose, the actor would have had an excellent chance of surviving.

2) Know the signs: Don’t let them sleep it off

While it’s not clear whether Hoffman had company when he stopped breathing, he could only have been saved if those nearby had known the signs of overdose and intervened.

If someone has taken any kind of depressant drug— including alcohol, benzodiazepines like Xanax or Ativan or painkillers— and they seem to be breathing unusually slowly, letting them “sleep it off” could be fatal. These drugs are far more likely to be lethal when taken together than when taken alone. In fact, most opioid overdoses actually include a combination of other drugs, including alcohol and anti-anxiety medications, that further depress breathing to dangerously low levels.

If someone has taken these drugs and starts “snoring funny,” or seems to have a bluish tinge to their skin and will not respond when you try to wake them, it’s a medical emergency. Call 911 and then start CPR with rescue breathing. Although chest compressions can be used without rescue breathing for heart attack victims, this does not work in case of overdose— what kills them is a lack of oxygen, so rescue breathing is imperative.

3) Know about naloxone

Although opioid overdoses typically take several hours to kill, once breathing has slowed past a certain point, it takes just seconds for the lack of oxygen to damage the brain irreversibly. But there is an antidote that if used before this point — even when the opioids are mixed with other drugs— that can instantly reverse what excessive amounts of the drugs can do, typically reviving victims in seconds.

That drug is known as naloxone (Narcan). The government’s Substance Abuse and Mental Health Services Administration (SAMHSA) is currently distributing an “Opioid Overdose Toolkit” [PDF] to encourage communities to learn about overdose symptoms and increase its availability. If you have an addicted family member or know someone at risk for overdose, the kit provides information on how to get it. Naloxone is nontoxic and cannot be abused— in fact, it causes unpleasant withdrawal symptoms so there is little likelihood it would be misused, and even less chance it would encourage more drug use as an overdose “safety net.”

MORE: Naloxone could cut overdose deaths by 50%

While the Food and Drug Administration (FDA) is considering making the drug available over-the-counter, right now, it’s only available with a prescription. So most people who could benefit from it do not have it handy when seconds count. It is not clear why the agency has not moved more quickly, given the level of public concern about overdose, but part of the problem has to do with the fact that naloxone must be injected, and that requires a certain amount of training to ensure the drug is delivered safely and appropriately. The National Institute on Drug Abuse funded a trail of a nasal spray version of naloxone made by Lightlake Pharmaceuticals, however, that reported positive results last December.

SAMHSA is also working to get the drug to more police, firefighters and other first responders— as well as those who are addicted, and their loved ones. However, because drug users often fear arrest, many do not call for help during an overdose, which is why some drug experts advocate for both expanding availability of naloxone, as well as changing laws to protect those who call in overdoses. At least fourteen states — including Washington, New Mexico, Florida, Maryland, New York and New Jersey — have “Good Samaritan” laws that provide at least some degree of legal immunity from drug possession charges for people who call for help when they see an overdose.

MORE: How the Drug Treatment System Failed Cory Monteith

To prevent more deaths, these laws need to be expanded. And the FDA should act quickly on the positive clinical trial results involving intranasal naloxone. It’s possible to save lives from overdoses. Why wait?

TIME Marijuana

Muting Marijuana’s High: Pot Without the Impairment

As legal sales of marijuana begin in Colorado, researchers have discovered a natural hormone that can block the drug’s high.

The hormone, known as pregnenolone, is already sold over the counter as an anti-aging supplement, since it is a precursor to steroid hormones like estrogen and testosterone, which decline with age. The new research suggests it could treat people with marijuana use disorders — as well as alleviate symptoms related to accidental or over-doses of the drug.

In the study, which was published in Science, the researchers found that pregnenolone is part of a feedback loop that regulates the the brain’s cannabinoid receptors, which bind to marijuana’s main active ingredient, THC. Mice given high doses of THC produced more pregnenolone, and this ultimately blunted the response of the cannabinoid receptors, preventing them from producing a high. Because pregnenolone affects cannabinoid receptors indirectly, it did not block all of the effects of THC. But it may inhibit all of the known effects associated with misuse of the drug— like memory problems and craving for more.

“The parts that are shut down are the ones that mediate many of the effects of cannabis that you may want to get rid of,” says Pier Vincenzo Piazza, one of the study’s authors and lab director of the Magendie Neurocenter at France’s INSERM research institute, “One is memory loss, another is [reduced] motivation and the third is seeking for the drug.”

The researchers tested whether pregnenolone levels rise with use of other drugs—but while they do increase slightly, the rise is nothing compared to the change seen with marijuana, so they think the effect is probably specific to THC. They also wondered whether pregnenolone contributed to the tolerance— or the need for more drug to get the same effect— linked to THC, but the doses of THC needed to make pregnenolone rise naturally were far higher than those that marijuana smokers typically ingest.

“It’s an intriguing study and the data look very convincing,” says Daniele Piomelli, professor of anatomy, neurobiology, pharmacology and biological chemistry at the University of California in Irvine, who was not associated with the research.

MORE: Marijuana Compound Treats Schizophrenia with Few Side Effects: Clinical Trial

While the findings might also suggest a way to maximize the benefits of marijuana for medicinal purposes, the researchers say that because pregnenolone also blocks THC’s pain relieving activities and food cravings, it’s not likely to be useful for medical marijuana patients with cancer or other conditions in which the drug might be used to alleviate pain or increase appetite. However, it might help those who use marijuana to benefit from its other active ingredient, cannabidiol (CBD), which has anti-seizure and anti-psychotic properties. By blocking the THC high, it could potentially allow these patients to use natural marijuana without entering states of of altered consciousness.

The agent might also be useful in treating users who become anxious or paranoid from THC. “This drug could be used as treatment of a cannabis ‘bad trip,’” says Piazza, “Some people, even without [taking a high dose] have very bad effects and find themselves in the ER with very strong paranoia and anxiety. This compound could help get rid of this.”

Pregnenolone does not actually prevent THC or the brain’s own cannabinoids from reaching their receptors by physically blocking them— instead it changes the way the receptors react. This is a new mechanism that might also make it useful for people with marijuana addiction.

Drugs that currently completely block receptors often have distressing side effects because they prevent both marijuana and the body’s natural neurotransmitters from acting, meaning that they can eliminate everyday pleasures, as well as those from drugs. For example, a drug that blocks cannabinoid receptors called rimonabant, which was briefly sold in Europe as a diet pill, turned out to cause depression, anxiety and other psychiatric side effects and had be withdrawn from the market.

When Piazza and his colleagues compared pregnenolone to rimonabant in mice, they found that while rimonabant increased anxiety, pregnenolone did not, suggesting that it might be useful in preventing unwanted effects of THC, but not the desirable effects of the natural neurotransmitters. That might help cut craving for marijuana while preserving other pleasures and motivations.

MORE: Viewpoint: How Marijuana Decision May Signal End of Drug War

While marijuana is less addictive than drugs like alcohol, cocaine and heroin, it is the world’s most popular illegal drug— so the roughly 8% of users who do develop problems with compulsive use are a tempting market for drug developers. As a natural hormone, pregnenolone is de-activated by the gut as well as rapidly transformed into chemicals like estrogen and testosterone when it does get to the brain, so it would probably need to be injected, not taken orally, in order to be effective against THC.

Piazza and his colleagues have formed a company, Aelis Farma, in order to develop an oral version of the compound that would not be metabolized into steroid hormones. Like rimonabant, it might also have potential uses for metabolic disorders like diabetes.

He is also aware that if he’s successful, there might be more controversial uses for his drug, such as neutralizing marijuana’s effects in order to get behind the wheel of a car after a hit. Such DIY uses may not be as reliable, he says, since the drug may not work completely in suppressing marijuana’s cognitive impairment if people don’t wait long enough for the treatment to take effect.

Still, such a rapid “buzzkill” could be incredibly useful. And while it’s a long way from mice to men, pregnenolone suggests the idea of marijuana without the high is not just a pipe dream.

TIME Coma

Viewpoint: Why Brain Death Isn’t An On-Off Switch

Jahi McMath
Jahi McMath Courtesy of McMath Family and Omari Sealey / AP

Thirteen-year-old Jahi McMath was declared brain dead after complications arising from a tonsillectomy, raising new questions about how we define brain death, and whether it’s time to revise our understanding of when brains can be revived, and when they can’t.

During her surgery, Jahi went into cardiac arrest, and a lack of oxygen to the brain that resulted in her brain death. She is being kept alive by a ventilator, but according to laws in all 50 states in the U.S., brain dead patients are considered deceased. Her doctors, and a judge in California, where the teen remains at Children’s Hospital in Oakland, concluded that McMath’s brain is unlikely to recover but her parents are fighting the hospital’s plans to disconnect her from life support equipment.

In cases like this— or those like the now eight-year-long coma endured by former Israeli prime minister Ariel Sharon and the skiing injury that has left Formula One champion Michael Schumaker comatose for nearly a week— everyone wants bright lines. We want to know if the person is conscious and suffering— and whether he or she can make a meaningful recovery. The rare but real cases where people do awaken from what doctors have labeled as brain death or irreversible coma only make the questions, and the need for answers, all the more urgent.

But the science of consciousness is far from black and white. For one, as philosophers have long noted, we don’t even know how to define it: I know that I’m conscious, but there’s no way for me to reliably determine whether you are a zombie or a robot, even if I can image your brain. Is awareness of one’s surroundings, and the ability to respond to stimuli, consciousness? Or does consciousness imply something more? When does a baby become conscious? Is my cat conscious? No one really knows.

Only recently have we begun to understand how anesthesia blots out awareness— and even now, in about 1 in 10,000 cases, people do become conscious of the pain and paralysis they experience during surgery, without anesthesiologists being able to detect the problem and increase the medication.

What we do know, however, is that consciousness is not merely something that is present or absent. One recent study, which I wrote about for TIME, for example, explored people’s responses to random sounds like clicks or those that have meaning, like words, as they were given increasing doses of an anesthetic drug:

At low doses of propofol, they stopped responding to the clicks, but remained able to identify words. This reflects the fact that the brain’s level of arousal isn’t simply related to objective factors like the loudness of a sound; instead, it’s the meaning of what you hear that the brain registers. A meaningless noise like a click isn’t enough to cut through the increasing drowsiness being caused by the drug, but an important word that may require attention can.

“Probably your name is most salient verbal stimuli you hear,” says [Emery] Brown [professor of computational neuroscience at MIT], “You can recognize it across the room in a noisy cocktail party.” He notes that when performing surgery, he makes sure to ask the patient what they prefer to be called so that the medical team can use the name most likely to arouse the person when needed.

MORE: Study Suggests Way of Preventing Patients from Waking During Surgery

Similar findings emerged when scientists studied the brain activity of Ariel Sharon, the former Israeli prime minister, during his coma. Although he has never woken up, he showed normal brain activity on an fMRI scan when listening to the voices of his family members compared to when those voices were scrambled into meaningless sounds. But does that mean that he was in some way conscious? Perhaps, as Dr. Nicholas Schiff, professor of neuroscience and anesthesiology at Cornell noted when we discussed this topic previously, it might help to think of consciousness as more of a spectrum rather than an all-or-nothing state. In fact, there are clearly levels of awareness, not just “aware” or “unaware.” “Consciousness is a brain process. It’s not an on-off switch, it’s an emergent property,” Schiff said.

That’s the latest thinking among neuroscientists about what distinguishes conscious brain activity and unconsciousness. They are also realizing that consciousness doesn’t seem to be entirely localized to any specific brain region. While some areas are clearly more important than others, people don’t lose automatically lose consciousness when one particular brain area is shut down, but rather when multiple regions are disconnected from each other. How many connections need to be severed before consciousness becomes impossible— and which ones matter most and where— are questions that experts like Schiff are investigating.

MORE: Waking the Unconscious: The Latest Science on Awakenings

All of this means that finding a completely reliable indicator of the ultimate lack of consciousness— death— is difficult. While some cases actually are black and white— there is simply no measurable brain activity at all in any region for long periods of time— the question of how to determine this remains a challenge.

For patients who fall into a coma, for example, the longer the coma lasts, the less likely the person is to regain any type of awareness. But even in these cases, there are exceptions, as researchers found recently that some people who had been in comas for years could be awakened simply by being given the drug Ambien.

Such uncertainty makes cases like McMath’s all the more challenging, since it provides her family even a tiny sliver of hope. The wide range of outcomes, and the extent of unknowns about the brain, complicates medical decision making and undoubtedly adds to both financial and emotional costs. Could more patients showing some signs of brain activity be awakened by the right dose of a drug like Ambien at the right time? How do we know when to let go?

When our brains are functioning properly, we can appreciate the fact that it is a complex and perplexing wonder. But when they’re not, we tend to forget the intricacy with which they are built, and yearn instead for certainty and simplicity. Understanding the continuum that is consciousness may help us to reach a deeper understanding of what awareness is, how injury and disease can affect these states and ultimately, how to move patients safely from lower to higher states of consciousness.

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